Good day, and thank you for standing by. Welcome to ProQR Therapeutics, the Axiomer Opportunity Conference Call. At this time all participants are in a listen-only mode. After the speaker presentation there will be a question and answer session. To ask a question during the session you need to press star one on your telephone, please be advised that todays conference is being recorded. If you require any further assistance please press star zero. I'd now like to hand the conference over to the speaker today, Sarah Kiely. Please go ahead. Thank you, operator. Good day, everyone. I am Sarah Kiely, Vice President of Investor Relations and Corporate Communications at ProQR. We are very pleased to share with you today an update on our Axiomer RNA editing platform technology following the recent partnership announcement with Eli Lilly and Company. Briefly, some logistics. This webcast can be accessed under the events section of our website at www.proqr.com and will be available for replay later today. The slides for the webcast can be downloaded from the webcast player or directly from our website. I would also like to bring your attention to the live captions that are available for this event. We will first go through our presentation and will then open the call for questions. In order to include your question on today's call, we request that you call in to the telephone numbers provided in the press release announcing this call. During the call today, we will make forward-looking statements. There are risks and uncertainties associated with an investment in ProQR, which are described in detail in our SEC filings. On slide three, you will find the agenda and today's speakers. Daniel de Boer, our founder and CEO, will open the call with some brief remarks, providing an overview of the Axiomer opportunity. Gerard Platenburg, our Chief Innovation Officer, will review the Axiomer platform in more detail with Bart Klein, our Senior Vice President, Innovation, providing an overview of our IP portfolio around Axiomer. Following our prepared remarks, Smital Shah, our Chief Business and Financial Officer, will join Daniel and Gerard for the Q&A, after which we will conclude the webcast. I will now hand the call over to Daniel. Thanks, Sarah. Good day, everyone. We're pleased to share with you an update today on our Axiomer RNA editing platform technology. Since the inception of our company, ProQR has been focused on RNA technologies that allow us to develop potentially life-changing medicines for patients with high unmet need. Today, we have a pipeline of several clinical-stage programs for genetic eye diseases. At the basis of our development pipeline lies a robust scientific organization that, in addition to discovering new programs for genetic eye diseases, is also exploring new ways to use oligonucleotides to target otherwise untreatable conditions. We've made significant scientific advancements, including the discovery of several RNA editing technology platforms, of which today we will elaborate on the Axiomer platform technology. In 2014, we started to work on Axiomer at the ProQR labs and filed our first patents on the first generation of Axiomer. Since then, we have advanced the science, built out an extensive IP portfolio, and generated the scientific expertise and know-how around this exciting platform to create medicines for patients in need. The Axiomer opportunity is significant, as it can be applied to more than 20,000 G to A mutations. ProQR's core strategy is to develop medicines for genetic eye diseases. For therapeutic applications of this platform outside of the eye, our strategy is to selectively enter into partnerships like the one we announced with Lilly yesterday that help to advance and capture the full potential value of the platform. Beyond Axiomer, we have another RNA editing technology platform called Trident. With this technology, we can make similar but different edits to the RNA, editing U's into pseudo-U's, which allows for the selective suppression of nonsense mutations or premature stop codons. This group of mutations accounts for approximately 11% of all disease-causing mutations that are known today, and Trident can potentially result in medicines for those mutations. At a later time, we will share more about the Trident technology, and today, we will focus on Axiomer. ProQR has a deep pipeline with four clinical stage programs based on a variety of different mechanisms of action, of which two are currently in pivotal stage. Our most advanced program, sepofarsen for CEP290-associated LCA, is on track for its phase II-III pivotal readout in the first half of next year. Beyond our four clinical stage programs, we have a deep pipeline of dozens of earlier-stage preclinical programs for other genetic eye diseases, of which a few are depicted on this pipeline slide. Our partner programs are depicted at the bottom of this slide. Earlier this year, we announced a partnership with DRL Biotechnology, a company incubated by RTW, on an undisclosed non-ophthalmology target. We have now announced our first partnership around our Axiomer platform technology with the exclusive license of up to five targets to Lilly. Lilly has a powerful development organization and has significant experience with innovative RNA science, making them a great first partner for our Axiomer technology. Under the partnership, we will work with Lilly on up to five targets to potentially benefit patients with genetic disorders in the liver and nervous system, where ProQR will drive the discovery phase and Lilly takes the lead on the development and commercialization. This partnership provides significant value to ProQR, where ProQR will receive $50 million upfront, including an equity investment of $30 million. ProQR is also eligible to receive discovery, development, regulatory, and commercial milestones totaling up to $1.25 billion, plus royalties on potential product sales. This transaction is a significant milestone for ProQR, providing a valuable endorsement of our technology, platform, and capabilities, as well as substantial funding. We're excited about this partnership and look forward to working with Lilly to create medicines for patients. It's now my pleasure to turn the call over to Gerard Platenburg, ProQR's Chief Innovation Officer and my co-founder. Gerard has decades of experience in RNA science and is a widely acknowledged leader in the field, having been involved with several important advancements in the field, including putting the first exon-skipping drug into clinical trials. Beyond being responsible for all discovery efforts that underlie our clinical pipeline, Gerard was also instrumental in the discovery of the Axiomer and Trident platforms. I will now hand the call over to Gerard to walk you through our Axiomer platform. Thank you, Daniel. I am very proud to be able to spend some time today shining a spotlight on our Axiomer platform, which was invented in-house at ProQR. Axiomer, as you will see, allows the use of synthetic editing oligonucleotides, or EONs, to change selected adenosines very specifically into inosines in RNA. This has tremendous potential for application in therapeutic development for genetic diseases, for currently there is still no treatment. The scientific field has been exploring the potential of oligonucleotides for several decades now. Back in the 1980s, it all started with ASO or gapmer mediated knockdown of targeted messenger RNAs. With this technology, it is possible to degenerate entire strands of RNA that may cause disease. The next step in the evolution of RNA technology following in the 1990s with exon skipping or splice modulation. With this technology, it became possible to cleave out the exon from the RNA that contains the disease-causing mutation, creating a shorter but often functional messenger RNA. With RNA-based editing, we are now taking it to an even more precise level. Our Axiomer and Trident-based editing technologies have very broad applications. We will focus mostly on Axiomer today and touch on Trident later. Axiomer is a very powerful RNA editing platform enabling us to use the same modality of synthetic oligonucleotides to specifically make changes at the base level in the RNA, correct mutations, or even to change properties of proteins. We do this using the machinery that is already present in human cells, called ADAR. Adenosine Deaminase Acting on RNA and its genes were first discovered in 1987. ADARs induce adenosine into inosine RNA editing, which is one of the most common forms of RNA editing. ADAR is able to both modify and regulate the output of messenger RNA, as inosine is interpreted by the cell as guanosine. ADAR has also been determined to change the functionality of small RNA molecules. Recently, ADARs have been discovered to act as a splicing regulator with their editing capability or RNA binding function. The post-transcriptional modification of mammalian transcripts in the central nervous system by Adenosine-to-inosine RNA editing is an important mechanism for the generation of molecular diversity and serves to regulate protein function through messenger RNA recoding. A-to-I RNA editing of the glutamate-gated ion channels is the most extensively studied. In fact, the first target of A-to-I RNA editing discovered in the mammalian system was the AMPA GluR2 subunit messenger RNA, in which a genomically encoded glutamine codon, a CAG, was changed to an arginine codon, or the AG. This edited Q/R site determines the ion permeability of the glutamate channel. Channels that contain the edited R form are less permeable to calcium. Essentially, the body uses ADAR in this context to create different isoforms of the glutamate channel to regulate calcium transport. There are numerous other examples of RNA editing taking place in our bodies. A-to-I RNA editing is a very frequently occurring natural process. Our Axiomer or oligonucleotide-directed RNA A-to-I editing platform was evolved on the mechanism from what nature was developed. Certain double-stranded RNA targets are engaged by ADAR, as you can see on the left side, and a specific adenosine is deaminated, resulting in an inosine. On the right side, you see that ProQR created synthetic editing oligonucleotides based on what we saw in nature. This mimics the double-stranded RNA target sequence that is recognized by endogenous ADAR, which is then able to deaminate a specific targeted adenosine. This corrects the mutation or can be used to diversify the function of the targeted messenger RNA. This allows us to recruit endogenous ADAR and make edits in the RNA where we want. Turning now to ProQR's Axiomer RNA editing platform. On the left, the Axiomer RNA platform technology enables single A-to-I editing in RNA using an editing oligonucleotide or EON to attract endogenous machinery to a targeted adenosine. Invented at ProQR, we have focused to establish the ground rules for EON design and develop strong IP protection with our current portfolio of 11 patent families. This, combined with a very strong KOL base in this field, positions us well for further development of this promising technology into the clinic. G to A mutations make up half of the SNPs that are associated with human disease. Therefore, this platform has huge potential to treat currently untreatable diseases. The high potential of the Axiomer platform for therapeutic development is based on two key pillars. Firstly, Axiomer uses synthetic oligonucleotides, which builds on the tremendous wealth of knowledge generated over the last four decades. Because the platform uses oligonucleotide manufacturing, chemistries are readily available. Much is known about targeted delivery of oligonucleotides to the organs such as liver, kidney, CNS, and eye, facilitating development strategies in those organs. Secondly, using endogenous ADAR machinery allows that the Axiomer RNA editing technology to avoid the use of complex delivery vectors, has a reversible mode of action, and acts only where the target is expressed. With this technology, we combine innovative technology with a modality experience of the last four decades. The Axiomer technology can induce A-to-I editing in all RNA, and therefore can be used in a wide range of applications. Firstly, Axiomer can potentially treat genetic diseases by reversing G-to-A mutations. This way it's possible to repair the genetic defect at both the RNA and protein level. Examples of such applications can be found in repairing splicing defects or correcting premature stop codons or SNPs causing defects in certain proteins. Over 20,000 G-to-A mutations are known to cause human disease, so the value of this approach is tremendous. Secondly, by making compensatory and de novo A-to-I or G changes, Axiomer has the potential to make subtle changes in RNA and thereby adjusting protein expression or function. This is just the tip of the iceberg of this very promising technology. The genetic medicines field has made great strides in recent years. We believe Axiomer has a unique and attractive proposition in the field of genetic diseases. With Axiomer, we are using our body's own systems such as ADAR to correct mutations only in affected cells, where the messenger RNA is expressed. As the machinery for editing is already in the cell, the editing oligonucleotides that recruit ADAR don't have to be complex molecules that need to be packaged, but are essentially the same as other single-stranded oligonucleotides. This makes delivery possible to a wide variety of organs. Using synthetic oligonucleotides, we ensure the therapeutic effect is seen as long as we would be dosing. No long-term effect of potential off-target editing is expected. Moreover, we don't have to overexpress the editing machinery or genes in cells. Axiomer-based editing can be applied across a wide variety of target genes, and here you have a taste of what that looks like. During our technology development, we were focused on understanding the ground rules to harness endogenous ADAR using EONs, and have explored this in many genes, of which a few are displayed in this slide. As you can see, EONs can induce A-to-I editing at high efficiencies in various systems, resulting in therapeutic levels of editing. Now the time has come to take this fantastic platform into therapy development. Axiomer has the advantage of using a proven modality. That means the oligonucleotide with established functionality in different organs of the body. Axiomer has, with a vast number of disease-causing mutations, the possibility to create medicines in all important disease areas. As an example, select number of disease targets that could be amenable to Axiomer in various organs are listed on this slide. Indeed, in addition to the rare monogenic diseases, also non-genetic diseases that affect large populations can be served using our Axiomer platform. With our announced Lilly collaboration, we are proud to share we will be starting to develop up to five targets in the liver and nervous system. Combining our pioneering RNA editing platform with the development power of our partner will propel our Axiomer platform forward. Aligned with our corporate strategy, Axiomer allows ProQR to fully exploit this RNA editing technology in the development of medicines for genetic eye disease. There are many. We anticipate that there are more than 1,100 targets in the genetic eye disease that are amenable to Axiomer RNA. In the coming 12 months, we plan to announce more details on the next targets ProQR will pursue with Axiomer. With the alliance with Lilly and a wealth of ophthalmology targets, this is an exciting time for our Axiomer platform. The broad application and a large number of unincumbent targets create a significant opportunity for further value creation through additional partnerships in therapeutic areas that are non-core to ProQR's strategy. I will now turn over the call to Bart Klein, our Senior VP Innovation. Bart has played an instrumental role in the discovery of our Axiomer technology, and with his background as an IP lawyer for over 25 years, he ensured the robust IP position we have built around Axiomer, which he will now provide an overview of. Bart? Thank you, Gerard. I'm pleased to share an overview of ProQR's IP estate around Axiomer and ADAR-mediated RNA editing. ProQR filed a total of 11 patent families covering the key features of the Axiomer technology. There are two general categories of patents with some overlap. First is covering the concept of recruiting endogenous ADARs with guides that possess a separate ADAR recruitment part, which can be a stem-loop structure or any other structure, such as an aptamer, with affinity for ADAR. The second category is patents covering guide designs with EONs that bring desired pharmacological properties such as metabolic stability, target-based specificity, catalysis by ADARs, and a variety of chemical modifications in the oligonucleotide backbone and/or bases. In summary, the Axiomer IP estate protects all the foundational elements of the platform using endogenous ADAR for therapeutic purposes beyond 2040. The design rules for editing oligonucleotides in terms of the chemical modifications that are preferred and/or tolerated in each position in the EON have been established. These modifications and modification patterns are portable from one sequence to another and are therefore target independent. We have patented these features independently of a target-specific IP and we refer to these patents as the platform patent. Mentioned earlier, there are 11 patent families covering these platform features. The colored circles represent the nucleobase sequence, which is determined by the sequence of the target RNA. The pentagons represent ribose, which can be modified to bring desired properties such as metabolic stability and editing specificity. Finally, the linkages between the nucleobases are represented by sticks with different color coding, indicating that different linkages have been tested for performance and subsequently patented. These linkage modifications are important for pharmacological properties such as metabolic stability and cellular uptake. These are properties independent of the nucleobase sequence. The table lists the modifications that we patented found to be preferred and/or tolerated. As you can see, we defined and patented the use of and the design rules, including all standard background chemistries used in the oligonucleotide field. Beyond chemistries, we also covered the stereopure forms for the linkages, where modifications would introduce a chiral center, such as a PS and PN linkage. These are the 11 patent families that cover the foundational features of the Axiomer technology, the platform patents. As stated before, the features covered by these patents are target independent. The special case is family with docket number 32, which covers a base modification of the cytidine sitting opposite the target adenosine in the target RNA when in double-strand RNA formation. This base modification, when applied in this so-called orphan position, improves adenosine flipping into the catalytic center of ADAR, leading to a three to four-fold increase in editing efficiency compared to guides comprising a non-modified orphan base. All filings have been published except the youngest, with docket number 39. The earliest file patents have already been granted in major jurisdictions such as the U.S. and the EU, as indicated in the last column. The others are in various stages of examination and are expected to proceed to grant due course. In summary, ProQR's Axiomer IP portfolio is strong. It is broad and provides coverage for the foundational features of the technology beyond 2040. I will now hand the call back over to Gerard. Thanks, Bart. As we have developed this technology platform, we have benefited from our relationships with several renowned scientific advisors, including those on our Scientific Advisory Board. Here, we have combined decades of oligonucleotide chemistry, delivery, and development knowledge with top science in RNA editing space. Art Levin has been helping us since day one and has four decades of RNA therapy development experience. Phil Zamore was one of the inventors of siRNA and a co-founder of Alnylam, and has been an important advisor on our RNA editing efforts and broader RNA science. Martin Maier spent considerable time both at Ionis and Alnylam and is a valued member of our SAB with significant translational science expertise. Peter Beal is a world-renowned expert in ADAR, and we work with him and his lab on optimization, understanding structural biology in relation to our Axiomer platform. Professor Yi-Tao Yu is a collaborator on the other RNA editing technology called Trident that Daniel briefly touched upon earlier. At Professor Yu's lab, pseudouridylation is a focus, and we are pleased to collaborate with him on this approach. In summary, we are extremely pleased with this validation of our Axiomer technology through partnership with Lilly and look forward to a productive relationship. ProQR will focus the platform to develop Axiomer-based therapies in the genetic eye disease field, for which we will announce our development projects in the next 12 months. Our Axiomer platform, with tremendous applications, will form the basis for additional value-creating partnerships. I thank you all for your interest in today's call. I will now hand over the call to the operator questions. Operator? Thank you. As a reminder, if you wish to ask a question, you need to press star one on your telephone. To withdraw your question, press the hash key. Once again, press star one for a question. Your first question comes from the line of Josh Schimmer from Evercore. Please ask a question. Hey, I think that's me. Thanks so much for taking the question and congrats on this partnership. Hoping maybe you can discuss the advantages or disadvantages of targeting RNA over DNA. Hi, Josh. Thanks. Obviously, there's a lot happening in the field of base editing and genetic medicines. I think DNA and genetic editing in general is really coming of age, and it's getting to the point that it's ready for development. The RNA technology that we are developing, Axiomer, has some unique features that allow us to target very specific individual bases that we can change out for other bases that allow for essentially reprogramming of a messenger RNA, which is done in a non-permanent measure. We can do that without having to touch the DNA, which obviously has some advantages from a safety and as a practical perspective. We think that for a large number of these applications, there's a very interesting case to be made for RNA editing. Great. Thanks very much. Thanks, Josh. Thank you. Your next question comes from the line of Dae Gon Ha from Stifel. Please ask a question. Great. Good morning. Thanks for taking my questions. Congrats on this deal as well from me. Two questions maybe for Daniel de Boer or even Gerard Platenburg. In terms of the proof of concept data, I was just going back to some of your earlier deck and saw that proof of concept data had been presented for the IDUA, the Hurler syndrome mouse model, and in vitro. Can you maybe elaborate on what other proof of concept data that you have generated to date, that may have culminated in this deal? Secondly, kind of related to Josh Schimmer's question, I guess looking specifically at the Axiomer versus some of the other ADAR technologies that are available today, maybe for Gerard Platenburg, can you maybe explain a little bit about the differentiation between Axiomer versus ADAR? Perhaps it's just based on the EONs and the technology there, but, if you can elaborate on that'd be great. Thanks, and congrats again. Thanks. Yeah, Gerard, can you address this question, please? Thank you very much. I think the proof of concept data that we are addressing in, I believe it's slide number 18, shows you that we have made quite extensive editing in several systems. We've progressed from there on as well. As you can see for alpha-1 antitrypsin on the CETP-001, we also got some very nice editing going on, and we also have, which we have not disclosed yet, but we have certain editing, in, let's say, IMD, inherited metabolic disease targets. That's something that we will build upon going forward to the future. We have progressed from there, and we will be focusing now together with a partner on certain liver, which are not disclosed, and also nerve system targets, so to speak. As to your second question, I think there's several technologies out there that are going after ADAR editing We can say that there's certain schools out there which express, let's say, hybrid proteins that are hybrid between ADAR and other proteins that target the editing activity, using also a guide sequence, and those are expressed from AAV. Let's say that's for instance, for Wave Life Sciences, the other schools that are using, let's say, oligonucleotides to recruit endogenous ADARs is quite similar to our approach, as well as for, as far as we know, for Korro Bio. I believe that some of the other companies where they, for instance Shape Therapeutics, they are using approach where they are going for endogenous ADARs, which then would be recruited by express, a more structured RNA guides. There's different schools out there that go after the RNA editing as dictated by ADAR. I hope that answers your question. Thank you. Your next question comes from the line of Jon Wolleben from JMP Securities. Please ask your question. Hey, good morning, and congrats from me as well on the partnership. Just one on logistics. Can you discuss your responsibilities under the deal with Lilly and whatever you're responsible for in either the early work or handing off the technology? One on the technology. Can you discuss delivery in a little bit more detail on how that might change depending on the target condition? Yeah Jon, thanks. Happy to address those. In the partnership with Eli Lilly and Company, ProQR Therapeutics will take responsibility of all the RNA science, the discovery, and the design of the molecules. We'll then work with Eli Lilly and Company in the early development and hand it over for clinical development to Eli Lilly and Company, where they take full responsibility and execution of all the clinical development and the commercialization. With respect to delivery, I think a major advantage of the Axiomer platform technology is that we, as Gerard Platenburg had mentioned in his slides, are building on four decades of RNA science. These oligonucleotides are essentially the same modality as all the other oligonucleotides that we have seen over the four decades being developed in terms of chemistry, in terms of size, in terms of manufacturing and therefore, also in terms of delivery. That means that the editing oligonucleotides we are developing for Axiomer can be delivered to all the same organs as other oligonucleotides are applied. Obviously, there's quite some experience out there with getting into some of these key organs that we're targeting here. That's helpful. Thanks again for taking the questions and congrats. Thanks, Jon. Thank you. Your next question comes from the line of Emma Nealon from Cantor Fitzgerald. Please ask your question. Hi, thank you for taking the question. In a disease like Crigler-Najjar syndrome, that also has CNS involvement, I guess just curious what the advantages are over a gene therapy approach and the ability of Axiomer to cross the blood-brain barrier more broadly in nervous system disorders? Yes. Gerard, please go ahead. Yeah. I'm afraid I didn't get the first part of your question, but if you say that the capability of Axiomer to cross the blood-brain barrier, I would say that like Daniel just alluded to, the fact that our EONs or Editing Oligonucleotides follow kind of the similar path as for other oligonucleotide-based modalities. For the, let's say, CNS component, we will be looking at specific delivery to the brain, for instance, by using intrathecal delivery or even direct ICV delivery. I hope that answers your question. Great. That's helpful. Just one follow-up. Have the five targets covered by the collaboration been pre-selected by Lilly? I'm just curious if there's any other restrictions around future partnerships in liver and nervous system disorders. Yeah, Emma, let me address that. The targets have not been fully identified yet. We've agreed a certain period for us to work through that. Beyond that, there's no major restrictions for future partnerships. We think there's a significant opportunity to do other similar partnerships on other targets. Thank you. Thanks, Emma. Thank you. Once again if you wish to ask a question please press star one on your telephone. Please ask your question. Keay Nakae, please ask a question from Chardan. Thank you. Yeah, just wanted to go back to delivery. For the liver, are you intending to use GalNAc? I think- Okay. Yeah. Oh, sorry. Go ahead. For the liver target, we intend to explore several routes, but among which there will be a GalNAc approach, yeah. Okay. I know you kind of answered this question for the CNS, but intrathecal would be, at least for now, maybe the preferred method of delivery? I'd tend to agree with that. Yes. Okay. Great. Congrats. Thank you. Thank you, Keay. Thank you. Your next question comes from the line of René Wouters from Kempen. Please ask your question. Yeah, thanks for the presentation and congrats on the collaboration from our side as well. First question is, what kind of news flow can we expect from the Lilly collaboration, going forward? Do you think that they will or you will announce when targets have been selected, pre-clinical progress, any color on that would be helpful? Yeah, thanks, René. Obviously the information that comes out of the partnership and what we disclose from that at the discretion of Lilly. We can't provide specific guidance on that at this moment in time. However, the Axiomer platform as a whole will progress over the year and the years to come. In the next 12 months from now, we plan to announce additional targets that we intend to develop ourselves in the genetic eye space. That is probably a next milestone for the platform to watch out for. Got it. A follow-up, can you provide a rough split for the development, regulatory, and commercial milestones that you indicated? With what kind of event do you expect to receive the first milestone? Yeah, good question. We can't go into detail there. We haven't disclosed that. In more broader terms, I think it's well distributed throughout early discovery, early development, later development, regulatory, and then some in commercial, with royalties on top of that. There is near-term milestones to be expected in the early phase of this partnership. Good. Thank you very much. Thank you. There is no more questions. This concludes today's conference call. Thank you for participating. You may now disconnect. Speakers, please standby.