Without doubt, the grand and collaborative experiment that was the mRNA COVID vaccine contributed mightily to the pandemic response and continues to save lives untold. It also demonstrated the collective power of public/private partnership in biopharma. Having acknowledged that, no first iteration of a new technology is ever the best iteration of that technology. On this week's episode of the Business of Biotech, we welcome Carsten Rudolph, Ph.D., co-founder and CEO of a company that recognizes this room for improvement. Ethris is developing mRNA-based candidates for the treatment of respiratory viral infections and rare pulmonary diseases, in addition to mucosal, multivalent, and mutation-agnostic prophylactic vaccines. Dr. Rudolph explains the concept, the business case, and how he's navigating Ethris toward a better treatment and vaccine paradigm in the wake of the pandemic.
You've listened along for years -- now you can watch along, too! Go to bioprocessonline.com/solution/the-business-of-biotech-podcast, where you can put faces to voices as you watch hundreds of interviews with the world's best biotech builders. While you're there, subscribe to the #BusinessofBiotech newsletter at bioprocessonline.com/bob for more real, honest, transparent interactions with the leaders of emerging biotech. It's a once-per-month dose of insight and intel that you'll actually look forward to receiving! Check it out at bioprocessonline.com/bob!
Without doubt, the grand and collaborative experiment that was the mRNA COVID vaccine contributed mightily to the pandemic response and continues to save lives untold. It also demonstrated the collective power of public/private partnership in biopharma. Having acknowledged that, no first iteration of a new technology is ever the best iteration of that technology. On this week's episode of the Business of Biotech, we welcome Carsten Rudolph, Ph.D., co-founder and CEO of a company that recognizes this room for improvement. Ethris is developing mRNA-based candidates for the treatment of respiratory viral infections and rare pulmonary diseases, in addition to mucosal, multivalent, and mutation-agnostic prophylactic vaccines. Dr. Rudolph explains the concept, the business case, and how he's navigating Ethris toward a better treatment and vaccine paradigm in the wake of the pandemic.
You've listened along for years -- now you can watch along, too! Go to bioprocessonline.com/solution/the-business-of-biotech-podcast, where you can put faces to voices as you watch hundreds of interviews with the world's best biotech builders. While you're there, subscribe to the #BusinessofBiotech newsletter at bioprocessonline.com/bob for more real, honest, transparent interactions with the leaders of emerging biotech. It's a once-per-month dose of insight and intel that you'll actually look forward to receiving! Check it out at bioprocessonline.com/bob!
The business of biotech is produced by LifeScienceConnect and its community of learning, solving and sourcing resources for biopharma decision makers. If you're working on biologics process development and manufacturing challenges, you need to swing by bioprocessonlinecom. If you're trying to stay ahead of the Cell or Gene Therapy curve, visit cellenginecom. When it's time to map out your clinical course, let clinicalleadercom help, and if optimizing outsourcing decisions is what you're after, check out OutsourcePharmacom. We're LifeScienceConnect and we're here to help.
Matt Pillar:Considering that about a month ago the CDC reported that just 8% of US children and 21% of US adults were up to date with the latest COVID-19 vaccine, which at the time had been available for a few months, it's no surprise I brought the virus home from the JPMorgan Healthcare Conference. Between COVID fatigue and vaccine hesitancy, getting into the COVID vaccine game right now might, at face value, seem like a bad business move. That is if you're coming at the COVID vaccine game from the same perspective Moderna and Pfizer BioNTech did back in 2020. But maybe if you bring a new vaccine paradigm to the population, you'd find that COVID fatigue and vaccine hesitancy are actually the driving forces behind commercial acceptance of your product.
Matt Pillar:I'm Matt Pillar, this is the Business of Biotech and I'll never knock the incredible result of the public-private partnership that we saw during Operation Warp Speed. But to cut to the chase, there's room for improvement on many fronts. We all know the first iteration of new technology is never the best iteration of a new technology. I won't put words in his mouth, but Dr Carsten Rudolph, CEO at Ethris, agrees with at least some of this sentiment. Otherwise he wouldn't be taking his company down the path of developing intranasally administered and inhaled vaccines and therapeutics for a number of respiratory indications, COVID among them. I caught up with Dr Rudolph in San Francisco to tape today's episode. Let's give it a listen.
Matt Pillar:That's where I want to start. I want to start with a little bit of background on where you came from and how you got into this space. Obviously, I did a little bit of research. I trolled your crowd up on your LinkedIn profile a bit and I learned that you have a pharmaceutical degree and have, quickly on the heels of that, you dove into the mRNA space, at least it appears that way.
Carsten Rudolph:Yeah, yeah, what does it mean? Quickly, I did my PhD exactly at the Department of Epidemiology, at Pediatrics, basically in Munich, yes, and at the Ludwig-Marsimius University. My PhD, I was mostly focusing on creating, developing a gene therapy approach for the treatment of cystic fibrosis, because cystic fibrosis, of course, is in our specialty or university pediatric hospital. It's a quite prominent disease. This was always my idea to do research and providing a new potential cure for these patients by delivering genes, of course, that replace the missing function in the body of these patients. But I was mostly working on non-biology and delivery. That means just using classmates and we all know. I think you're also a biologist, aren't you?
Matt Pillar:No, no, no, we should have set that record straight from the outset.
Carsten Rudolph:But then I'll give you a brief biology tutorial. You've got to toll the line here because I am not.
Matt Pillar:Listeners of the podcast know I've said it many times I dropped out of advanced placement biology my senior year of high school.
Carsten Rudolph:However, our audience will appreciate a little bit of flavor, but one real problem for using that's plasma DNA then, of course, is how to get the plasmid into the nucleus, Because the gene, of course, is active in the nucleus, sarah, and the lung tissue is a quite post-metonic tissue, so it's not fastly proliferating when the nucleus membrane breaks down, basically, so it's really a limitation. And then we thought, well, and we knew in those days basically that our delivery systems and model particles that we used, we could pretty well shuttle the messenger RNA into the cytoplasm. Yeah, so that worked quite well. And then we thought is there a nucleic acid, basically that you could make use for the turgis that is active in the cytoplasm? And of course there's the messenger RNA that can be translated at the ribosome to produce the missing protein. Then this wasn't the idea. Well, why shouldn't we use messenger RNA?
Carsten Rudolph:In those days no one was really doing a lot of work in this space here and we stuck it on this and we saw, well, that works really well.
Carsten Rudolph:They're much, much more efficient than using plasmids.
Carsten Rudolph:But we saw at the same time that just the standard messenger RNA molecule and we know this all now from the pandemic vaccine development as well is quite emogenic Because we have a lot of sensors in our innate immune system that is made for detecting these foreign RNA molecules, because this could signal just invasion of the virus, like the coronavirus, which is an RNA virus.
Carsten Rudolph:So we thought, well, it's very efficient, but it's also quite emogenic, basically. And then we thought, how can we navigate around this here? And then we thought about modifying the messenger RNA and introducing modified nucleotides, because we know from you, from the SIRNA field and the oligonucleotide field in those days, that if you do so you can really reduce the immune response and recognition of the RNA molecules. And then we played a little bit of ground and we found really a scheme where we can change the pattern of the RNA molecules so that is not recognized any more that well by their immune system. And then we thought, well, that works quite well, shouldn't we exploit this potential of such molecules? And then we started to find the problem here. So that was the idea behind it.
Matt Pillar:Yeah, that's why the question I asked you is you were talking about this research work and we like who was we at the time? Like pre-athrists, who have we?
Carsten Rudolph:at this. This was my research team basically at the Department of Pediatrics and my colleagues over there, and I shared the lab space with another professor and we were running those SIR experiments in these days here and then you know, I was always because we all know. You know that there RNA molecule itself, a negative RNA molecule, is not taken up by the sample SIR. It does not penetrate through the cell membrane and so you always have to package this, basically or the nanoparticles, and then taken up to release the mRNA payload in the cytoplasm.
Matt Pillar:Yeah, and.
Carsten Rudolph:I was always also intensely collaborating with now also my micro-founding partner of the company, christian Klang, who was running and a research group as a professor at the Technical University in Munich so that's their second large university in Munich and he is a really expert, well-leading expert in designing our carrier systems for nucleic acids. And then we thought basically, yeah, we can put this together, the expertise and turn it from the company and then after we got the first business angels convinced that then we were really brave.
Matt Pillar:Oh, no, we have to do it.
Carsten Rudolph:I will always remember this moment, this funny moment. So my plan was just something I want to become a full-time professor, basically, but now I became an entrepreneur?
Matt Pillar:Yeah, you brought it up, so now I want to dig into it. You made that decision. So many questions there. What was your biggest reservation? So you thought destined for professorship. And then you did this work and you realized well, there's the foundations of a biotech here. What was your biggest reservation about making that leap?
Carsten Rudolph:I would not say reservation, it was more a, basically because I always thought that if you do research here at the university here, this also should be something where you can, because I mean, this is basically the both tax money here at France that we raised there. That would be something that you have to give back also and make something useful out of it. So that was always my intention of my research that I did at the university. So we thought, no, we just have to try it now. And of course I mean, if we had failed, then there would be always the opportunity then go back to academia. So. But we thought, no, if we don't try it, then who will pick up those ideas that we develop? No one. So we thought no, we have to restart and do it by all.
Matt Pillar:That's how we did it.
Matt Pillar:That's great.
Carsten Rudolph:We now have the first program in the clinics. It took us some time. It's a complex thing to develop for a pulmonary messenger RNA therapeutic.
Matt Pillar:For sure, and we'll talk a little bit about that clinical program in a little bit. But from the business perspective it almost sounds like a bad joke. So two scientists are in a bar right Doing mRNA research. When you decided that you were going to launch a company, you said you didn't really have reservation because you knew that you wanted to make a contribution with what you learned. But building a company is a different thing from being a research academic, or professor, to that matter. So what? I guess maybe not reservations, but what were some of the early steps that you took around learning how to be at the helm of?
Carsten Rudolph:a biotech company and the first thing is to write a business plan. Basically that was the starting point and this was basically, I have to say, that was a trigger. Then, basically, you know, we had in Germany also business plan competitions, basically for young startups, and then we thought, OK, we try to just put down the paper, our thoughts, basically, and then you get, of course, structured thinking around yeah, so what you all need and what kind of value proposition, what kind of drug, and to start or to create a financial plan, budget and all these things. And there I think we self-trained ourselves mostly, I would say. And then we thought, yeah, we will try it now and we will do it and we will learn while we do it. So that was the starting point.
Matt Pillar:Yeah, did you have support resources? So like here in the States? You know I'm not sure what the biotech scene looks like in Munich, but here in the States you know oftentimes startups will take advantage of communities, incubators. You know even parent companies that spend biotechs on. So I'm just curious, like, to what degree did you have the opportunity to lean into folks who had founded biotech companies?
Carsten Rudolph:Yeah, so there was definitely some exposure, you know, because our first business angel who helped us also to move this forward and look into the right things that you have to basically consider yeah, so that was. And then there is, of course, I mean, also in Munich. You know we have a kind of small biotech hub there with their kind of infrastructure and this was also good when we got some exposure here to this sort of creating business.
Matt Pillar:Yeah, yeah, getting back to the science that you founded the company on, you said it started out with research and cystic fibrosis. Right Was the by the time you realized that you had something that was really building a biotech around. What was sort of your therapeutic intention at that time, like in terms of indications and targets, did you think, well, we can move this well beyond where it?
Carsten Rudolph:started. Yeah, it was always this. Focusing to the pulmonary space, you know, because that's where I have my home, my scientific home, so to speak, and where I knew this field very good, the biology and, of course, the exposure to our thinking of what you have to consider for delivery, etc. So and with I mean there are really a few severe diseases, therapeutic diseases, where there's not a good cure available. Yeah, so we thought, no, that's a good place to go. Basically, I mean, we did also some work in those days in bone regeneration, you know, to locally translate our proteins that are in grafted oncology and sponges to induce bone healing and non-critical defects, you know where bones are broken and they don't know anymore that they've been all together. So you have the help there with biology that we did also some work in this space. Basically, but mostly we decided to look and go into the lung space.
Matt Pillar:Yeah, okay, remind me what timeframe this was. What was after this?
Carsten Rudolph:So we started to look into using messenger RNA. That was roughly around the 2006-2007 timeframe, yeah, and we followed the initial most important patterns of our technology in 2009,. Yeah, and then we started the company towards 2011,. Yeah, basically and really truly operational we became in 2012,. Yeah, it's pretty much 10 years from now, yeah.
Matt Pillar:That's, I mean relative to the recent, I guess, advance in awareness and even growth, just in terms of the industry and the number of companies who are playing in this space. Those were early days.
Carsten Rudolph:Yeah, those were the very early days and also, you know, in the academic setting, basically there was pretty I mean, I think, pretty much a lot of the birth of the messenger RNA drug modality. I think this was came really from Germany, yeah, so we had the longest there. I think that were our colleagues from QVAC, basically, I think more, who were the first one who tried to develop messenger RNA for cancer vaccines. Then we had Hugo Schahe in the same time, the founder of BioNTech, who you were thinking of, developing messenger RNA for the cancer treatment, and it was us basically, I think, to develop our pulmonary therapeutics. So this is all roughly in that timeframe, basically, yeah.
Matt Pillar:Yeah, what's fascinating in those early days. You mentioned your business angel your angel investor From there to sustain the company and to grow the company. What was the investment scene like in this therapeutic modality in those alley days?
Carsten Rudolph:It was tough, basically because there was not this awareness of messenger RNA. Now everyone knows what messenger RNA is. Of course, in those days they were rather not. There was also a time where the SIR RNA therapeutics there were waves. It goes up and down. There were sometimes some into the SM and then I remember a time when Roche stepped out of their SIR RNA. Then there was again less appetite. Then it took a little bit again to create the awareness. But this was early. It was really entirely new in those days.
Matt Pillar:So how did you, as an academic and founding the company with an academic beyond that angel investor, how did you learn to navigate the biotech fundraising scene? What did you do in those early days to maintain Speak with a lot of?
Carsten Rudolph:people yes, speak with a lot of people. Basically they are going to meetings, to conferences to find investors. That's what we then also found, basically our first investors. We then basically invested with the company so that we could really do the first steps.
Matt Pillar:Did you see a spike in interest from the investment community during COVID?
Carsten Rudolph:Yes, I think so Because of the awareness that we got from the mRNA space. I think it's very important for the theater. In the end of the COVID pandemic there was a nightmare for the world, but for mRNA it's a great success. It could be shown that the full potential of messenger RNA that you can develop really fast drug products. Most important, we have approved our mRNA vaccines. It's also now clear that this is a new drug modality that can achieve a proof of that. I think that's very important for the entire field. Now we have so many new great areas where people now explore the potential of messenger RNA. It's a new drug modality that's fantastic to see.
Matt Pillar:Events like that obviously a global pandemic is going to have an impact on biotech, not just in terms of the repercussions that we saw accessibility of raw materials and outsourced capacity, that kind of thing. But it can also alter the course of the company's pipeline ambitions. We saw it in COVID. There were hundreds of biotechs that didn't have COVID therapeutics.
Carsten Rudolph:Suddenly we had a little bit of the same policy. We embarked on one program at the beginning of the pandemic. We're with a partner, a company in Switzerland, nurengun, which are incredibly knowledgeable in identifying human antibodies. We teamed up, basically, and then, from the first patients that were accessible to them, they isolated and identified a really super potent human, a patient-derived antibodies. The idea was that we translate the protein code into an mRNA code which can then be inhaled and you produce the antibody in the lung directly at the site of virus infections, so that you have, to speak, a protective level, a level of layer of antibodies covering the lung tissue.
Carsten Rudolph:We could nicely in those days hamsters were used as a model and we could nicely reduce and avoid this weight loss that you experience after infection with SARS-CoV-2. We moved this pretty far. But then what happened? All in the sun, and that's what we also know, this virus changes its face quite rapidly and then, when we reached the Omicron level, basically, of mutation, we then unfortunately saw that the antibody was not neutralizing the virus anymore. So we unfortunately had to terminate that program.
Carsten Rudolph:So that's for one, and the second one is basically, you know, the program that is now moving in. The ball is in the clinics now. We just started the first phase one trial just before Christmas. This also a little bit goes back basically to the pandemic time because you know that's the concept, eth 47, where we have a method, rna that encodes for a type III interferometer, and these type III interferons in the lung are called, yeah, it is capable of programming the epithelium in a very broad antiviral state which interferes with replication basically of any respiratory virus. That's a very broad activity, this molecule. And this basically goes also back to the pandemic time because we've got a big funding for this program from the Bavarian state, yeah, so who were looking in those days not only to put the bet on only vaccines, because no one knew in those days will the vaccine make it, but we also need therapeutics basically. So in the end the pandemic had an influence on what we did.
Matt Pillar:Yeah, it sounds like a win and a loss. Maybe A bigger win than loss. Yeah, absolutely, biger win, definitely. What was your pipeline structure before those two opportunities presented?
Carsten Rudolph:Yeah, just mostly centered only on rare pulmonary diseases. So that's still a focus of our company, because for a program here, what I just mentioned, eth 47, this is a program where you need really a partner with the Global Footprint app to develop this drug basically, but it's a small biotech company. We really want to become a fully integrated biotech company that develops manufacturers and sells its own drugs, and that, of course, is something you can achieve in a space where you have a very decidable patient population that you can serve by yourself, the biotech company, and that's, of course, the rare disease space. So this was always our goal and that's why we've looked at our major focus is on rare genetic pulmonary diseases.
Matt Pillar:So it's interesting. It seems the exception to the rule of late. Like most of the companies that I've talked, most of the CEOs that I've talked to are very clear about their intentions, and it's decidedly not to build their own manufacturing facilities and become an integrated biopharmaceutical company.
Carsten Rudolph:Okay, if you, in the end, fully manufacture everything in-house, that's a different question. You can use, of course, wonderful CDMLs that's what we do right now but we established all the manufacturing processes in-house. And that's also important, you know, because we have for pulmonary drugs you have rather higher doses than for vaccines. So we always looked very early on in creating and developing our easily scalable manufacturing process. So we have our narrow process developed that is not based on HPLC, so it's just built on tangential flow filtration, which is easily scalable Now, and also the advantage that it's purely APS, no solvents involved, and this is what we transferred to CDML. We worked with a fantastic CDML there together manufacturers, our drug product.
Matt Pillar:Yeah, I'm interested in your perspective on the explosion of the RNA, anything RNA space. We'll stick with mRNA, but I mean you can put any letter you want in front of it, right? Yeah, yeah, in a COVID and post-COVID world, and I mean, I think about it like you've been working on this. You know science and this technology since you know the mid-2000s and before, and for years and years.
Matt Pillar:I'm not going to say it's going unnoticed, but it's not necessarily, you know, in the media cycle, and then all of a sudden this pandemic happens. And then, on the heels of the pandemic, it's like being the only person in the world who thinks the color blue is cool, or even knows about the color blue, and then, all of a sudden, overnight, like everyone's- like blue is awesome.
Matt Pillar:We love blue, right I?
Matt Pillar:mean there had to be. That had to be kind of a you had to be aware of it, right, and like the explosion of interest and explosion of companies. I mean, there's so many companies in this space right now, so what's your take on that Like.
Carsten Rudolph:It's great for the field. I mean, it's fantastic. So the more approaches we see, the better we get here. And there are so many diseases that can be potentially treated with messenger in A. This can't be done by only one party basically. So that's great that we have so many different approaches here, not only for the vaccines. So I think we will see some new potential approvals rather shortly, also for additional vaccines or in infectious disease space. But also look into the cancer space here. I think we see really very nice good signals in this space where people use messenger RNA as a drug fidelity. But then look into genome editing. There is a great potential for messenger RNA to be used here. And I mean we have the first success now for CRISPR being approved, crispr technology. So that's a huge step basically and I think a huge stimulus also for moving this forward with using messenger RNA. Basically.
Carsten Rudolph:And then, of course, there is this field of rare genetic diseases where we see, I think, pretty good programs also for liver genetic diseases and of course we want to achieve the thing with our pulmonary programs there and to really offer hopefully as soon as possible some help for the patients suffering from these diseases. So I think there's not really moving forward right now.
Matt Pillar:Yeah, in the context of your pulmonary focus, what do you see as the biggest potential risk to progress? But whether it's a technical risk or a market risk or a scientific risk, what's the rate limiting factor or big risk that could stand in the way of progress?
Carsten Rudolph:I mean, in the end it's always the basic concept of developing a drug and this all centers around right biology you have to really understand your biology then right exposure, so that you have the right PK, you know that your drug gets there where it needs to be for the right time basically. Then, of course, pretty good, the right safety. That's all the basis of a successful drug in the end. And then and that's what you mentioned is there the right patient? You have to understand your patient, basically and then the right commercial. So I think it's a kind of umbrella, basically, that you have to look at and go into very detail for each of these elements basically and we did this for PCD, for primary sedatives, canisia we believe that we hit those boxes basically. So we tackle very interesting biology because in those patients who suffer from the disease, they are miscellaneous proteins that drive the motility of the tiny airs and our lungs and our airways that are responsible for moving the mucus out of the lung. Yes, that's called mucosilir escalator and it's made to remove any dust that we inhaled from the lungs so that we have a fully particle-free surface of the lung. But what is important to understand here is that these CDR, they are just made by the airway cells, once in the cell life and in the half-life of the airway.
Carsten Rudolph:You said something like four to eight weeks and that means you can imagine if you're delivering a messenger RNA during the cediation process, quite persistent effect. So if you translate a quite short lift drug itself the mRNA is gone in the lung after two and a half days, something like this, into a quite persistent effect. And so we believe that's a good starting point from the biology and that's why we, for instance, picked the PCD the patients. It's a very clearly defined because it's a genetic mutation. So you take this risk out of it, basically of the explosion. We know that we need to potentially restore the CDR function in about 20% of the CD8 cells. We believe that's doable on what we see in our preclinical studies and there is a commercial potential because it's a life-limiting disease basically, and it's a high unmet need because there are no drugs on the market. So that's why we believe that's a good spot for messenger RNA computing.
Matt Pillar:I mean I could go down a rabbit hole here. Am I hearing you correctly? You talk about this cellular regeneration like a cycle and you're saying that there's an efficacy opportunity at a specific point in that cycle.
Carsten Rudolph:No, you just have to restore the function. Basically once the CDR are restored, you have a quite persistent effect Because the cell does not change the CDIA, so it's once built and then they work until the cell is removed from the body and replaced by a new cell. For the lifetime of the cell Gotcha.
Matt Pillar:OK, see, these are the questions I should have been asking in AP biology before I dropped the class.
Carsten Rudolph:My senior year.
Matt Pillar:Not long ago I had your senior director of formulation and aerosol research done on a live event that I hosted for Bio Process Online, christian Domen.
Carsten Rudolph:Great guy, by the way. He is fantastic.
Matt Pillar:I tell you, yeah, absolutely yeah he was super valuable, just brought a whole lot of wealth and wealth of information to that conversation. But one of the things that we talked about quite a bit on that during that conversation was LNP stability and some of the challenges around there. So is that, do you see that as potentially a rate limiting factor?
Carsten Rudolph:I see that this limitation in the field, because I mean just look into the commercialized vaccines, mrna vaccines there. So first we see that they need very cold temperatures to be stored and that was OK during the pandemic basically. But now we move into the post-pandemic phase and we really want to have temperatures that the pharmaceutical industry is used to use and also for the patient. So that means this overall cold chain needs to be improved and need to be overcome, and I think we have done a lot here with our technology where we can contribute to this and achieve this.
Carsten Rudolph:But with our technology we have, for instance, the livalization process in place where we see that we can store the drug product already for a year in the fridge, two to eight degrees, and the studies are ongoing, but we don't see any change here. And even at room temperature you see this already for more than half a year. So that's, I think, a huge step forward. And then also you have to see and look into the stability of the drug product itself. Look, the commercialized vaccines are ready to use drug product so it can be used for chemo-laws basically. And we have with our SNAPs what we call our LNP. So we have already achieved six days at room temperature. That means doctors can now really plan for using the drug for an entire week. So I think that's a large improvement. And on top we have developed our recall and stabilizing XEPian technology here.
Carsten Rudolph:Those are a certain class of excipients from the inactive ingredient list from the FDA. That's what you can add to the LMPs and you make them mechanical stable. And why do I mention it? Because on the label of the commercial vaccines that's mentioned don't check them because they are very prone to aggregation, basically. So and we can really now stabilize these nanoparticles so that you can even vortex them and shape them at full speed and we don't see any changes in the particles. And of course this gives you confidence to also the doctors and pharmacists to use the drug, because they don't have any concerns anymore that might potentially aggregate, and also for manufacturing. You know, when, in particular, the philipinibus step, these nanoparticles flow through little tubings to basically go into the bile, then of course you have to avoid aggregation, to avoid any batch failures. So I think that's really important, what we have achieved here. And then I think another I mean, when we speak about limitations, I think another limitation maybe and I think that's a little bit unspoken also in the field is that there are.
Carsten Rudolph:You know the pronunciations from the commercialized vaccines they biotip, distribute to the entire body. Yeah, from the documents, from their authorization, you see that 30% goes into the liver, it goes into the heart even if you just locally inject the muscle. Yeah, and even 2 to 4% of what's found in the plazas found in the brain, basically, and we think if you don't need it in the brain, one should not deliver it to the brain, basically, and you know our SNAPs that are Seems logical.
Carsten Rudolph:Yeah, okay, and you know our SNAPs that are made from catechonic lipidoids, not catechonic lipids. They are a little bit more positively charged so they can package the messenger RNA more tightly, so you need just half of the formulation but they lead to a full retention of the mRNA drug at the site where you deliver it. And that's of course so you can avoid this biotip distribution. And this is you know for us for our pulmonary drugs that we develop. We want to have the full activity of the messenger RNA, of course at the site where it's needed, that means in the lung, and avoid any biotip distribution. It's also safety aspect of that. So that's why we think really we have achieved pretty much here to move the field in our products also really forward with the advantages and to try to overcome those limitations that we just spoke about before.
Matt Pillar:Yeah, what's been your experience with the? I guess on the regulatory scene. So I have conversations with my colleague, anna Rose Welch, who's leading a new project that's going to be called Advancing RNA right now and we often talk about, you know, some of the uncharted regulatory waters in this space, so what's been your perception there? I?
Carsten Rudolph:mean, I think overall all the regulators are really very, very educated now from the commercialized vaccines. I think that's a great step, but you know what I think for the field it would be very helpful, but that's ongoing already. The other is to consider a kind of platform approach, so where you can more easily, if you leave everything the same and your drug formulation, the mRNA formulation, but just then replace this with another messenger RNA, so that you get there certain efficiencies.
Carsten Rudolph:Exactly, exactly, so this is for us also very important this approach, because these primary cellar dyskinesias they are not caused by a lack of acidic fibrosis, by only a mutation in one gene, but there are more than 50 genes known, when mutated, that can lead to primary cellar dyskinesia, because you can imagine this is a very complex proteinaceous apparatus. To get this beating ongoing, and for us it would be very helpful to swap out one messenger RNA for another messenger RNA to then serve another genetic mutation that causes the disease. So those things that would be really helpful, but I think that's a lot of thinking into this direction already.
Matt Pillar:Yeah, yeah. When I look at the ATMP, space, cell and gene therapies, there's a lot of bad news. I mean there's a lot of consternation about accessibility and cost and even commercialization. I mean there have been some not so smooth approvals in terms of commercial access how does the mRNA field collectively ensure? I mean, obviously with the COVID vaccine it was sort of a non-issue, right, we all got our shots. But how does the mRNA world, as it addresses more complex indications and perhaps charts some complex manufacturing waters, how do you make sure that you're not making some of those same? I don't even want to say mistakes, but trying to maintain an efficiency that results in patient accessibility at the end of the day, I think you're referring to those gene therapies that were upfront.
Carsten Rudolph:You paid a few millions basically for a treatment. And I mean the situation, I think, with messenger RNA drugs is a little bit different because it's more like a standard drug that you repeatedly administer to the patient. So I mean for our PCD programs. Basically, we believe that's a little bit into the direction that you see for cystic fibrosis, where you have already the pricing then here on the market.
Matt Pillar:So you don't anticipate any indications where that cost control might become a factor.
Carsten Rudolph:If you use messenger RNA or possible genome editing, that means a one-time treatment and then you are done. Basically you face the same problems. But I think also the people start to think creatively how to solve this. What you mentioned, yeah, how can we find financial models basically that we can also serve those patients suffering from these rare diseases? Because in the end, for one rare disease just a few patients, but if we sum up, all patients that suffer from all the genetic, no rare diseases that we have, those are many patients basically, and I agree with you. But I believe that the field is looking into creative reimbursement models because we have to find a solution there, because we want to provide medicine to these patients as well. But for the mRNA I think it's a little bit different because it's not a one-time treatment, or at least what we do, and then you fix it, but it's those like standard drug basically.
Matt Pillar:Yeah, very good. Just a couple more questions that I will need to wrap up, but I'd start with what? Give us a clinical update, what the next big steps for atherists are. What's on your immediate?
Carsten Rudolph:horizon? Yeah, exactly so. For us important and I mentioned this already for the first program we just started our first phase one study just before Christmas. So this is our study that has three arms basically One arm is where we deliver it into the nose and one arm is where we deliver it into the lung and then we will have, after defining their highest dose, basically a combined arm. And we do, of course, safety. That's their major clinical endpoint.
Carsten Rudolph:But we look into also targeted engagement, which is very important so that we can measure in nasal swabs and in sputum from these treated healthy volunteers, the production of their recombinant protein produced by the messenger RNA. And, more important, you know that we also see the downstream activation of the genes that are induced by the interferonamda, which gives us the indication it works, it is really doing what it is expected to do. And this is the study we will have completed towards springtime. So we think we will plan an interim readout towards early spring basically. So that's the first very important news that we expect then in 2024. And then afterwards we are also in the midst of putting the preclinical package together for finding a CTA towards autumn this year for our first PCD candidate, and so it's exciting time For sure, yeah, very good.
Matt Pillar:And then, just to wrap things up, when you come to an environment like a giant investor conference at this stage and atheroses sort of continual non-clinical bath, what's your MO here? What's your goal? What are you looking to make happen? Raise money?
Carsten Rudolph:No, seriously. I mean now we enter into the sort of clinical scene, basically, and then we need many more financial resources than before and that's our goal here at JPMorgan and also to fund partners, because we have a really powerful we believe best industry platform technology and of course this can also enable and help other potential partners to develop new drugs with our technology. So it would be great to leverage on top our technology also outside our focus area.
Matt Pillar:Basically, yeah, excellent. Well, I wish you well the rest of your time here and I appreciate you coming all the way from Munich solely for this opportunity to be on the business, of course, math yeah. Absolutely my pleasure. I enjoyed conversing with you and learning more about what Ethris is doing. Same here, Matt.
Carsten Rudolph:Many thanks for having me. Thank you All, right Very good.
Matt Pillar:I'm Matt Pillar and you just listened to the business of biotech, the weekly podcast dedicated to the builders of biotech. We drop a new episode with a new exec every Monday morning and I'd like you to join our community of subscribers at bioprocessonlinecom Apple Podcasts, spotify, google Player anywhere you get your podcasts. You can also subscribe to our Never Spammy, always insightful monthly newsletter at bioprocessonlinecom. Backslash B-O-B. If you have feedback or topic and guest suggestions, hit me up on LinkedIn and let's chat and, as always, thanks for listening.