ProQR Therapeutics N.V. (PRQR) Earnings Call Transcript & Summary

Thank you, operator, and good day, everyone. I'm Sarah Kiely, Vice President of Investor Relations and Corporate Communications at ProQR. Today, we issued a press release announcing findings from additional analyses from the Phase II/III Illuminate trial of sepofarsen and an update on our corporate strategy. This press release can be found on our website at www.proqr.com. With me today from the management team is Daniel de Boer, our Founder and CEO. Following his prepared remarks, we will have a Q&A session, which will include Daniel, along with Dr. Aniz Girach, our Chief Medical Officer; Gerard Platenburg, our Co-Founder and Chief Innovation Officer; and Smital Shah, our Chief Business and Financial Officer. [Operator Instructions] 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. I will now hand the call over to Daniel.

Thank you, Sarah. Good morning and good afternoon, everyone. Thank you for joining us on today's call. Today, we have announced some significant changes to our business. And on this call, we will further elaborate on our findings, the changes to our business and what the future will look like. ProQR is focused on the development of transformational RNA medicines, and we do this across 2 pillars. Our first pillar is to develop RNA medicines for genetic eye diseases. In this pillar, we recently had a setback with the announcement of the missed primary endpoint in the Phase II/III Illuminate trial of sepofarsen for the CEP290-mediated Leber's congenital amaurosis type 10. The second pillar is innovative RNA science with our Axiomer RNA editing platform technology that we discovered at the ProQR labs and have been working on since 2014, where we have been building a substantial IP estate, a strong partnership with Eli Lilly and compelling data in targets across multiple organ systems. Today, I will walk you through the acceleration and the expansion plan of this technology in the business update. I'll start with a high-level overview of where the business stands today. After which, we will delve deeper into these topics. Following the top line results from the sepofarsen Illuminate trial, we undertook a thorough investigation into the conduct of the trial where we concluded there were no critical issues or technical errors. In parallel, we have conducted post-hoc analysis of the sepofarsen Illuminate data, in which we have observed an efficacy signal similar to our earlier trials when we compared the treated eyes versus the fellow untreated contralateral eyes in the same patients. The European Medicines Agency, or EMA, the regulatory body in Europe, had suggested the use of this control in prior written and verbal communications. Given the visit-to-visit variability and the heterogeneity introduced by genotype, phenotype and eye potential factors, a parallel control group in a trial with small sample sizes is difficult. In order to globally harmonize the protocol, we decided at the time to proceed with the FDA requirements of having a parallel sham control group. We think this is an interesting finding, which we will further elaborate on, on this call. And we plan to discuss these findings with the regulators and provide an update on that in Q3 or early Q4, depending on the timing of these meetings. In light of these developments, our strategic priorities going forwards are to explore further development of sepofarsen and ultevursen pending the regulatory feedback from the European Medicines Agency, EMA, and the U.S. FDA; and secondly, to accelerate development of the Axiomer RNA-based editing technology platform. Accordingly, we have decided to implement some significant changes to our business to reprioritize our activities and pipeline and limit our spend. Subject to this regulatory feedback, the ultevursen pivotal program will be scaled back to a single trial, from which we plan to build in an interim analysis or futility analysis in 2023 to reduce and limit the at-risk investments in the program. We will suspend earlier-stage genetic eye disease programs and activities, including the QR-1123 and the QR-504a trials and all the discovery, nonclinical and translational activities related to genetic eye diseases. With these changes, we will reduce our workforce by approximately 30%, which will include our Chief Scientific Officer, Dr. Naveed Shams. I want to thank Naveed for his contributions to our company and look forward to continuing to work with him through our Scientific Advisory Board. In line with our strategic priorities, we will increase our focus on the Axiomer platform technology by expanding our efforts from previously 10% to 15% of the R&D workforce to now about 1/2 of the R&D teams to focus on Axiomer and build a platform out to generate the pipeline beyond the eye into the liver and CNS that can be developed in-house or with potential partners like Lilly, with whom we have a strong ongoing partnership. With the before-mentioned changes, we are extending our cash runway into 2025. None of these have been easy decisions. We have tried to balance all the stakeholders in our decision-making, and that includes: the patients and the patient communities that we aim to serve first and foremost; our employees, who have put in tremendous efforts over the years; and our investors who are funding the resources and for whom we also want to create long-term value. Now we will first focus on the update on sepofarsen since we read out the top line results from Illuminate. I first want to acknowledge that LCA10 is a devastating disease with very high unmet medical need that is affecting many patients and families. Patients with LCA10 go blind in the first few years of life, and there are no approved drugs that can treat this disease. Our preclinical and earlier clinical data, including some of the individual responder data, suggest that sepofarsen could be an important therapy for individuals that live with LCA10. So in an effort to understand what led to the miss in the primary endpoint analysis of the Illuminate trial, we did a deep investigation into the trial conduct to reassure ourselves that there were no technical errors in the conduct of the trial that could explain the surprising outcome. As expected, the trial was well executed with no material errors found in elements like the activity of the drug products, randomization, data handling and unmasking. We did find that one of the enrolled patients was a light perception patient who should have been excluded. Hence, this patient is excluded from all the analysis going forward, including those we will look at today. The bottom line is that no critical issues were identified and the primary analysis stands as it is. So looking at that data, as a reminder from the top line primary analysis, on the left-hand side, we see Best Corrected Visual Acuity, or BCVA, where we see the treated eyes in the first bar and the sham eyes from a parallel control group in the second bar. As you can see, there is not much of a difference between the 2 groups. And on the right-hand side, we see FST in 3 different wavelengths, where for each wavelength, we see the treated eyes in the first bar and the sham eyes in the second bar. Also here, we don't see much of a treatment effect of sepofarsen. Having seen the functional readouts, when we look at the patient reported outcomes, or PROs, and the investigator feedback, it seems that there is an effect of sepofarsen treatment. The first PRO is the PGI-C where patients treated with sepofarsen self-report, in 61% of the cases, to have experienced an improvement in vision, whereas only 25% in the sham group do. The second panel shows the VFQ-25 where we see the mean score of the composite questionnaire with a noticeable difference in favor of sepofarsen. The feedback we hear from investigators also suggests that patients are experiencing a benefit that is noticed by the investigators. This is inconsistent with the functional outcomes we saw at the mean level in BCVA and FST on the earlier slide as compared to the sham parallel control group. We also note that about 1/3 of the patients in the Illuminate trial were responders on multiple endpoints, which we also saw in a number of patients that had meaningful responses across multiple endpoints in our earlier trials. One of the key differences between the Phase I/II trial and the Phase II/III Illuminate study is that in the Phase I/II study we used the contralateral fellow untreated eye as a control, where in this trial, we used a parallel sham control group as a control. As LCA10 is a disease with a lot of heterogeneity, this can include a lot of variability, especially as this is a small sample size trial. Patients have days where they can see better than other days, which is a known phenomenon in ophthalmology. However, this visit-to-visit variability affects both eyes to the same extent. In the top right panel, we see an example of a sham patient where we see that both eyes perform in concordance with each other with some variability from time point to time point. On the bottom-right panel, we see a sepofarsen-treated patient with some variability also, but clearly, a separation of the lines in favor of the sepofarsen-treated eyes. In previous discussions with EMA, they recommended us to use the contralateral eye as a control, specifically for this reason. However, as this is a global trial, we harmonized the protocol globally to the FDA recommendation to use sham as a control. So to control for this visit-to-visit variability, we can look at the delta between the treated eyes and the fellow untreated contralateral eyes in the same patients. This is the so-called treated eyes minus untreated eye analysis or the TE minus CE analysis. As is depicted on this slide, we now see the same BCVA data as we saw earlier. On the left-hand side, we see the sepofarsen-treated group. The first bar depicts the treated eyes. The second bar shows the fellow untreated eyes in the same patients. And the third bar shows the delta between those 2 eyes. Now on the right-hand side, we see the same for the sham group. So the sham-treated eyes, the contralateral non-sham eyes in the same patients and then the delta between the 2. It is noticeable how the effect in the sepofarsen group sustains, where in the sham group, it mostly disappears. So now let's take a look at the rest of the Illuminate data through that lens. As we just saw, here we are looking at BCVA again. On the left, we are looking at the graph that we saw before of the change from baseline in the sepofarsen-treated eyes compared to the change from baseline in the sham-treated eyes. On the right of this slide, we are now looking at the treated minus untreated eye analysis. We see clearly that most of the perceived effect in the sham group goes away, while the benefit in the sepofarsen treatment largely remains. And on FST, we see the same effect. The top panel here shows the FST data that we saw earlier. The change from baseline in the sepofarsen-treated eyes compared to the change from baseline in the sham-treated eyes across the 3 wavelengths. At the bottom of this slide, we're now looking at the treated eyes minus untreated eyes analysis. Here, we also see that the effect in the sham group largely goes away, while the benefit in the treated eyes remains approximately the same, a very consistent finding with what we have observed in BCVA. We also note that this is in line with the self-reported improvement of the sepofarsen-treated patients in the Illuminate trial, and the anecdotes from the investigators on the benefit they observed for their patients. We will share this important filing with the scientific community in a few weeks at both the Annual Retinal Cell and Gene Therapy Innovation Summit and ARVO as it may have implications for other IRD trials. And we will also discuss the totality of the data with the regulators. This meta analysis is the totality of the BCVA data, shown here in the treated eye minus untreated eye analysis, where we now combine all the data from the sepofarsen-treated patients across the Phase I/II trial and the Illuminate Phase II/III trial. Given this is a post-hoc analysis, we don't know what the regulatory value is of this finding. But given the meaningful responses observed at both trials in several patients, their clear unmet needs and our very patient-centric approach, we think this is an interesting finding that we will discuss with the regulators in the near term. So in terms of our next steps, we will engage with the regulators on this topic and expect the first update from those interactions and any potential impact on the current plan in Q3 or early Q4, depending on the timing of these meetings. In the meantime, we will continue the ongoing Brighten and Illuminate trials as DSMC recommended that after reviewing both the safety as well as the efficacy data, we should continue, where they concluded that the safety and tolerability looks as expected, similar to what was seen in earlier trials. In the meantime, we will minimize the spend in sepofarsen, pending the outcomes of the regulatory meetings in Q3 and decide on potential next steps, either stand-alone or in partnership, after that. So looking beyond sepofarsen, how does this finding impact the rest of our pipeline? First of all, we think our data across multiple trials show that the contralateral eye may be a better control in small sample size IRD trials, and that this will potentially have impact beyond ProQR. We will share these filings with the scientific community at the Annual Retinal Cell and Gene Therapy Innovation Summit next month. And pending regulatory feedback, we plan to incorporate these learnings into our trial for ultevursen. Second, we are reassured on the underlying platform technology as our data suggests that the drug is active as we have seen in earlier trials. And the miss in the primary analysis is likely caused by a small n, an imperfect control and high variability, as is unfortunately often observed in ultra-rare disease drug development in small sample-sized trials with a heterogeneous population. So what does this mean for ultevursen? Ultevursen targets USH2A, retinitis pigmentosa and Usher syndrome, which causes a different disease compared to sepofarsen. USH2A leads to a high unmet medical need, and there is a very sizable patient population of at least 16,000 patients in the Western world. We think the data generated in ultevursen to date is compelling and is unaffected by the sepofarsen Illuminate readout. And on this slide, we see that data from the interim analysis in the Stellar Phase I/II trial that we have presented previously, showing consistent responses across multiple endpoints, including a robust effect on the objective measure of OCT imaging in the ellipsoid zone analysis. Now on this slide, we're zooming in on BCVA when compared to the contralateral eye. We see that after a longer-term follow-up, the observed effect is maintained, which increases confidence in BCVA as a primary endpoint in USH2A trials, which we are using in our ongoing Sirius Phase II/III trial. Having that said, we will incorporate the learnings from sepofarsen into the pivotal program by making some adjustments. First of all, to reduce our at-risk investment, we will scale back from 2 pivotal trials to a single pivotal trial by winding down the Celeste study in early to moderate patients, which is the more costly trial of the 2. Second, we will discuss with the regulators to amend the protocol for the Sirius study, which is targeting more advanced patients by switching from sham to contralateral eye as a control, and mitigating the investment risk by incorporating an interim analysis or futility analysis in 2023. We then expect to have full primary endpoint readout in 2024, which is well within the cash runway, which is into 2025. We will discuss these proposed changes to the protocol with the regulators in Q3 and come back with an update in further detail after that. So to summarize the changes that we are making to our portfolio, we will report back once we have discussed with the regulators the Illuminate post-hoc analysis in Q3. To limit our investment risk, we will wind down Celeste in ultevursen and plan to build in a risk-mitigating interim analysis or futility analysis in the Sirius trial, limiting the at-risk investment, which we then also plan to build in the lessons on the contralateral eye control from sepofarsen pending regulatory feedback. We also plan to report back on the regulatory feedback in Q3 of this year. In light of recent developments and in an effort to preserve capital and extend the cash runway, we will also spend further investments in all earlier genetic eye disease activities, including the trials in QR-1123, QR-504 and the discovery, nonclinical and translational activities related to genetic eye diseases. As a result thereof, we will reduce our workforce by 30%. And we'll shift the focus of the R&D organization, to a larger extent, to Axiomer. Before, approximately 10% to 15% of our R&D workforce was dedicated to Axiomer. After this change, about 1/2 of the R&D teams will focus on the Axiomer platform. This will allow us to accelerate the development of our Axiomer platform and pipeline both through in-house development as well as through partnerships like the one that we have announced in September with Lilly. As we plan to accelerate our Axiomer platform, you will hear much more about this platform going forward. As we, for example, presented new data last week at the RNA Editing Summit in Boston. As you know, our proprietary Axiomer platform technology allows us to selectively edit individual basis in the RNA. This technology recruits an endogenous system, which we can guide to a place in the RNA where we want it to edit. And we have protected this filing with over 10 patent families dating back to as early 2014 when we made the discovery. Axiomer can be used for reversing disease-causing G-to-A mutations in genetic eye diseases. In literature, there are more than 20,000 disease-causing mutations known across many different organ systems, of which some are listed here on this slide. This allows us to treat diseases that before we were not able to target. But Axiomer's capabilities go way beyond single mutations and genetic diseases. We can also use the technology to selectively edit wild-type RNA. This can be used to engineer proteins or modify their function. For example, by altering glycosylation or phosphorylation sites. This application has a huge potential in nongenetic and nonrare diseases. We are just starting to scratch the surface of what is possible by harnessing the Axiomer platform technology. As Axiomer can be used widely across so many diseases, we plan, in addition to our in-house development, to seek partnerships with others that allow us to capture the full value of this platform technology. As an example of that, we entered into a partnership with Lilly in September, under which we licensed 5 targets to them in the field of liver and nervous system. In exchange, Lilly paid us $50 million upfront, and we agreed on another $1.25 billion in milestones plus royalties down the line. The partnership is going very well so far and is unaffected by any of the events related to our genetic eye disease business as the teams are largely distinct and operate independently. As we have just licensed 5 targets in this partnership, the remainder of the platform remains unencumbered and could be used for additional partnerships in the future. Now looking at some of the data and the different therapeutic target areas. Over the years, tremendous progress has been made in the lab, and we are now accelerating the work on that basis. We have optimized our design rules and can now apply these across multiple targets, which cause diseases in multiple different organ systems. As you can see in this summary slide, you see editing into the high double digits across our therapeutic areas of interest, including eye, CNS and liver. And in parallel, we're doing work, in partnership with Lilly but also stand-alone, to further apply this to diseased targets and select development candidates in the near future. Importantly, we have protected this platform with a strong IP aspect. The Axiomer technology using endogenous ADAR to edit RNA, was discovered at the ProQR labs in 2014. And ever since, we have filed our discoveries in patents. We believe these patents now give us robust protection and make this technology proprietary to us. As we accelerate the Axiomer platform and expand our effort here, we will build out our strategy, both in-house as well as in partnerships. In-house, we will increase our efforts from approximately 10% to 15% of our R&D group to now about 50% of the R&D employees focused on Axiomer. Throughout this year, we expect several additional data updates and also the announcement of the internal development candidates, in addition to any progress that may get reported on the Lilly partnership. And we do expect a first IND in the next 18 to 24 months. On the partnership front, we are very pleased with how our partnership with Lilly is progressing. And we will continue to execute on that partnership as a key priority. We also see the opportunity to enter into additional partnerships to capture more of the platform value. And as we mentioned before, currently just 5 of the thousands of potential targets are out-licensed. So lots of potential to do other partnerships down the line. So in summary, the Axiomer platform has a strong value proposition, unparalleled leading IP position, the validation of an industry partnership with Lilly and robust data across multiple targets and therapeutic areas with a very broad platform applicability. Looking at our near-term priorities, we will prioritize and accelerate the Axiomer platform technology with now about 1/2 of our R&D workforce committed to that. We will explore the sepofarsen data with the regulators while we minimize spend on the program in the meantime. And we will amend the ultevursen pivotal program to a single Phase II/III trial with an IA or futility analysis in 2023 to limit the at-risk investment. Following the Q3 meetings with the regulators on sepofarsen and ultevursen, we will determine next steps for these programs and keep you updated. With the changes that we have announced today, we have extended our runway into 2025. And within that window, we plan to achieve many potentially value-creating milestones as we are listing here. The updates announced today are very sobering for us and show how difficult it is to develop drugs for ultra-rare diseases that are poorly understood. We have confidence in the updates that we provided today, and we look forward to continuing on our efforts to make an impact for patients in need. I want to thank our team of ProQRians and especially those employees who are departing us for their passion and their commitment. I want to thank our shareholders for their support through the years, the investigators for their collaboration and all the patients and their caregivers for their trust in us. Operator, we will now take questions.

[Operator Instructions] Your first question today comes from the line of Yigal Nochomovitz from Citi.

This is Carly on for Yigal. So you had mentioned that the contralateral eye analysis was actually suggested by the EMA. I'm more curious if there's actually any regulatory precedent for a contralateral eye comparison supporting approvals in ophthalmology either in Europe or in the U.S.

Thanks for the question. I'll let Aniz address that.

Carly, at least to my knowledge, I don't think there's any precedence for approval, although I know that many companies have had these kinds of issues that have gone to regulators in the past. But at least I don't see this as an issue in the past that I've encountered. Now, of course, gene therapy is very unique in the sense that gene therapy trials typically will be unmasked, typically, open-label studies, if they are subretinal injections, and therefore, they indeed may face similar issues in the future as well. And at least historically, I know from my previous experience in the gene therapy world, similar occurrences did occur.

Okay. Got it. That's helpful. And then we just had 1 question sort of on the strategy. Could you talk about why you have sort of more confidence in the early stage Axiomer platform and are shifting R&D dollars to that as opposed to continuing to pursue QR-1123, 504a and other IRD research? Is it just because of Illuminate? Or are there additional reasons why you may have less confidence in these other IRD programs?

Yes. Thank you, Carly. So look, I think what we've now found in sepofarsen is that the data suggests that a parallel sham control group in an ultra-rare disease like LCA10, where the heterogeneity is quite significant, introduces so much variability that using sham as a control introduces a lot of risk into those programs. And the other earlier-stage IRD programs that we have in the pipeline are exposed to that same amount of risk due to this parallel sham control group. So until we understand better how we can deal with this from a regulatory perspective, especially in the U.S., we have suspended those programs as they relate to the genetic eye disease pipeline. Now with respect to Axiomer, that platform technology is completely unaffected by any of this. Axiomer is -- as I mentioned in the prepared remarks, is a RNA-editing technology that can be applied very broadly, that can be used across multiple different organ systems for rare diseases, for genetic diseases, but those are for nonorphan, nongenetic diseases and kind of wide applicability beyond the eye. So we think that this is completely unaffected by any of the findings in sepofarsen for IRDs. And therefore, we think it's a really interesting opportunity with a very solid IP position, and a validation through an industry partnership and really encouraging data that has been presented over the last few months and years to further back up that platform.

Your next question comes from the line of Dae Gon Ha from Stifel.

Yes. Great. I guess 2 questions for us. First question is actually a 2-part question regarding the Illuminate reanalysis that you guys did. Very thorough. Thank you very much for providing that. I guess the first part of that is if we look at Slide 11, where you're showing an example of sham versus the contralateral eye, just kind of curious, the divergence in the 2 curves as it pertains to the contralateral eye in the sepofarsen example, why would that be? And I guess if you look broadly at the 24 or 23 patients that have received sepofarsen, I guess how many of them would follow the example that's shown on this slide? Because I seem to remember that the contralateral eye also benefits given the nystagmus effect. And then the second part of the sepofarsen question is, if we look at the reanalysis, you're showing about 0.12 LogMAR benefit. Can you remind us what the test/retest variability is on the BCVA front? And then maybe I'll follow up with the ultevursen question next.

Aniz, maybe you can address this question.

Yes. In terms of the response that we see in that slide 11, that's a -- there to be able to give an example of the principle with which we took the revised analysis, the post-hoc analysis. We know that, for example, 1/3 of the patients within this Illuminate trial responded on BCVA and multiple other concordant endpoints. And therefore, there is a significant number of patients that have got a benefit from this particular analysis. We will be sharing more information at the upcoming ARVO and also the genetic eye disease FFB conference later on this year. And so we'll reserve some more information for that, if that's okay. Your second question was related to the test/retest variability. We found that actually that's consistent with what others have found, that about a 0.1 LogMAR can be the test/retest variability. We do know that off-chart patients have slightly more variability. Luckily for us, the majority of our patients were on chart. And so that's really a consistent feature so far.

Okay. Great. If I can just stay with you, Aniz, on the ultevursen trial, you were talking about, I guess, now narrowing it down to just Sirius versus Celeste. So given your BCVA experience so far and what we know about microperimetry, I guess, being sort of the approvable endpoint for those that are more peripherally impacted, I guess, what was sort of the impetus for you to focus on the Sirius and the BCVA front, given the sepofarsen example versus kind of going with Celeste?

Yes. I think first thing to say is that from a mechanism of action and science point of view, the sepofarsen data and information doesn't really impact the ultevursen programs. We know that the ultevursen program is based on good science, good preclinical knowledge and is independent from sepofarsen. That's the first thing to say. And indeed, we've decided to discontinue the Celeste trial. The Celeste trial had as its endpoint, primary endpoint, static perimetry. And we know that that's associated with a lot more variability. And so far, there has not been a precedence for getting a drug approved with static perimetry as the primary endpoint. And if you think for the Sirius scenario, the primary endpoint there is BCVA. And we're maintaining BCVA without drug, seeing the natural history of the disease, allowing the deterioration of BCVA in the control arm. And so for us, that seemed to be much more derisked. And also, it's using a primary endpoint that's established as an approvable primary endpoint across the board with all agents. So it's really for those multiple reasons why we decided to discontinue the Celeste trial and continue with the Sirius trial.

Okay. Aniz, just to make sure I understood you correct, there is no precedence for approval based on the static perimetry on the 7-decibel [ 5-low ] side. Is that correct?

Correct. Exactly.

And your next question comes from the line of Jon Wolleben from JMP Securities.

A couple for me as well. I guess first on the post-hoc analysis, I didn't see any comments on dose response. I'm wondering if you observed any on -- any of the efficacy endpoints? And then with the patient-reported outcomes, looks interesting. Wondering if you could tell us a little bit more about the magnitude of benefit these patients saw. It sounded like you just mentioned they saw some improvement, but I'm wondering if you could characterize that a little bit further.

Thanks for your question. So on the first question on the dose response, as we often see with oligonucleotides, they have a very speed dose response curve. So it's almost an on-off effect. And I think that's what we've observed here. So all the doses we've tested so far have seen similar responses across the board. So we don't see much of a difference, hence, we presented the bold analysis. For your question on the patient-reported outcomes, I'll hand it over to Aniz.

Jon, the first thing to say is that we'll be sharing a lot more information at the ARVO conference coming up later this month and also the FFP meeting. But we did do a multitude of different PROs. The FDA recommended one was the PGI-C, which is the patient global impressions of change. And we know that about 61% of patients suggested that they had an improvement compared to roughly 25% in the sham control half. So there was an overwhelming number or proportion of patients who felt that their vision improved overall on the treatment compared to sham. In addition, we know that on the VFQ-25, the Visual Function Questionnaire 25, again, many more patients had an improvement compared to the sham. And that, coupled with the discussions with investigators, who investigators were saying that, look, when they've seen and observe their patients, and of course, investigators are still masked at this stage, they have identified those patients that are clear responders at this stage in their minds as they see these patients. And as we translate that into areas that we're unmasked to that data, we can see very clearly that there are patients in the sepofarsen arm that are clear responders there. And it's really for those reasons why we want to be able to go to the regulators to be able to discuss this data in much more detail. And indeed, like I said, we'll share some more granularity on all of those at the FFB meeting and also the ARVO meeting coming up this time.

That's helpful. Wondering if you've dosed any second eyes yet as well.

Yes. We have dosed second eyes of those patients who have been treated actively with the active dose of the one eye. And indeed, after the 12-month time point, even the sham patients have crossed over for dosing for bilateral administration. So indeed, that data is going to be very useful again to be able to present to the regulators in the future.

So Jon, as you may recall, this is formally a 24-month study. So the primary endpoint was at 12 months. But the patients are continuing on the trial of those 24-month time point. And indeed, the second eyes and the sham eyes will be treated in that second 12 months.

And maybe one more at a high level, Daniel. You mentioned -- you discussed genetic eye diseases and previously IRDs. Is there -- is that just semantics? Or is there a different group of opportunities here with this new focus? Or again, is it just semantics?

Sorry, you mean on Axiomer? Is there a focus outside of genetic eye diseases?

Yes. Are you still going to be focusing on inherited retinal diseases? Or is there another subset of eye diseases that fall under a broader genetic eye disease bucket?

No. So with our focus on Axiomer, we're going to focus broadly on the applicability of that in eye disease so not just IRDs, but genetic IRDs, but also in liver and CNS. So this is beyond IRDs. I think what we have noticed is that this variability that we have observed here will likely translate to other inherited retinal disease programs as well. So we first need to understand what the regulatory perspective is on how to mitigate that risk to be able to develop drugs for inherited retinal diseases. And on that, we will learn more in Q3. So pending that, we will focus on the 2 IRD programs that we have and further expand the Axiomer platform in parallel.

Your next question comes from the line of Steve Seedhouse from Raymond James.

This is Nick on for Steve. I just have a quick one about Axiomer. Can you just comment on the just general delivery methods that you intend to use with Axiomer? For instance, with liver indications, do you plan in using an LNP? Or how do you plan on taking care of that?

Good question. So look, with Axiomer, I think we're at the intersection of all the experience that was gained with oligonucleotide drug development over the last 4 decades, since the modality, a single strand of oligonucleotide is very similar to every other oligonucleotide that's known today, which means that from a delivery perspective, we can really apply all the lessons that have been learned. So for the liver, there's known delivery method through nanoparticles, but in particular through GalNA complications. And so they're a good proof of concept with approved products for delivery of oligonucleotides in the CNS space as well as for the eye. So we think we can really build on the lessons that were learned in oligonucleotide drug development and apply that to this really new mechanism of action of ADAR-mediated A-to-I editing using the Axiomer platform technology.

[Operator Instructions] Your next question comes from the line of Keay Nakae from Chardan.

Yes. In terms of your acceleration of Axiomer, if you think about which of your proprietary programs you might advance, should we think of those as, I guess, ultra-rare diseases as well in order to fit in within the time frame that you've laid out to get data? And if you're going to target something in the liver or nervous system where you have the licensing agreement with Lilly, do you have to show it to them first? Or you would you choose to proceed on your own with such a target?

Good question, Keay. So we are applying Axiomer to a wide variety of different targets, both genetic rare diseases, but also nongenetic diseases. And we can't really comment yet on what programs we will select to go into development. We do plan, by the way, to give people an update on that later in the year to let people know what we plan to do with our internal development pipeline. With respect to our partnership with Lilly, we've agreed for them to work on up to 5 targets in the field of liver and nervous system. And within that range -- within those therapeutic fields, we have agreed on the path on how to select those. So we are at liberty to select our own targets for our internal development.

Thank you. I will now hand the call back to Daniel.

I want to thank everyone for joining our call today, and we look forward to keeping you updated on our progress over the period to come. Thank you.

Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.