Q4 2023 Regenxbio Inc Earnings Call
Participants
Patrick Christmas; Chief Legal Officer; Regenxbio Inc
Kenneth Mills; President, Chief Executive Officer, Director; Regenxbio Inc
Stephen Pakola; Chief Medical Officer; Regenxbio Inc
Vit Vasista; Chief Financial Officer & Executive Vice President; Regenxbio Inc
Gena Wang; Analyst; Barclays
Gospel Enyindah-Asonye; Analyst; Morgan Stanley
Alec Stranahan; Analyst; BofA Global Research
Annabel Samimy; Analyst; Stifel
Danielle Brill; Analyst; Raymond James
Luca Issi; Analyst; RBC Capital Markets
Mani Foroohar; Analyst; Leerink Partners
Presentation
Operator
Good day, and thank you for standing by. Welcome to the Regenxbio fourth-quarter 2023 earnings conference call. (Operator Instructions)
Please be advised that today's conference is being recorded. I would now like to hand the conference over to Patrick Christmas, Chief Legal Officer. Please go ahead.
Patrick Christmas
Good afternoon, and thank you for joining us today. Earlier this afternoon, Regenxbio released financial and operating results for the fourth quarter and full year ended December 31, 2023. The press release is available on our website at www.regenxbio.com.
Today's conference call will include forward-looking statements regarding our financial outlook in addition to regulatory and product development plans. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted and can be identified by words such as expect, plan, will, may, anticipate, believe, should, intend, and other words of similar meaning. Any such forward-looking statements are not guarantees of future performance and involve certain risks and uncertainties.
These risks are described in the risk factors, in the management's discussion and analysis sections of Regenxbio's annual report on Form 10-K for the full year ended December 31, 2023, and comparable risk factors sections of Regenxbio's quarterly report on Form 10-Q, which are filed with the Securities and Exchange Commission and available on the SEC's website.
Any information we provide on this conference call is provided only as of the date of this call, February 27, 2024. And we undertake no obligation to update any forward-looking statements we may make on this call on account of new information in future events or otherwise. Please be advised that today's call is being recorded and webcast.
In addition, any unaudited or pro forma financial information that may be provided is preliminary and does not purport to project financial positions or operating results of the company. Actual results may differ materially.
I would now like to turn the call over to Ken Mills, CEO of Regenxbio.
Kenneth Mills
Thank you very much, Patrick. Good afternoon, everyone, and thanks for joining us. I'm pleased to begin today's call with a recap of our recent business highlights, as well as an update on our corporate goals. Steve Pakola, our Chief Medical Officer, will then provide an update on clinical programs; and Vit Vasista, our Chief Financial Officer, will provide an overview of financial results for the fourth quarter and the full year ended December 31, 2023. At the end of the call, we're going to open the line up for questions.
Late last year, Regenxbio began work on a pipeline prioritization plan that enables us to focus our capabilities and resources on large commercial opportunities where product candidates are differentiated, can be expedited, and support meaningful value generation soon and for the long term. Our priority programs are ABBV-RGX-314, program for the treatment of wet AMD and diabetic retinopathy being developed in collaboration with our partner AbbVie; RGX-202 for the treatment of Duchenne; and RGX-121 for the treatment of MPS II, or Hunter syndrome.
Early on in 2024, we've experienced exciting progress for each of these programs. We believe there's a multibillion-dollar potential for the 314, a single-injection treatment to become a first-in-class therapy in wet AMD and the standard of care to treat and prevent progression of diabetic retinopathy. Enrollment remains on track with our subretinal delivery program for wet AMD, currently in pivotal trials with an expectation to support global regulatory by the end of 2025 through the first half of 2026.
We hosted calls recently with leading retina experts to review our new positive clinical data from our treatment for wet AMD and diabetic retinopathy using in-office suprachoroidal delivery. These events were exciting for us. And today, we're going to be talking about additional upcoming data and events that we're giving guidance on.
Three weeks ago, we focused attention on our rare disease pipeline and two amazing milestones. In Duchenne, we announced the completion of enrollment in cohort 2 and additional positive interim data from our ongoing trial. We are thrilled to see RGX-202 is demonstrating strong microdystrophin expression across a wide range of patients.
And for MPS II, we achieved what I think is a major breakthrough, with statistically significant results for our pivotal trial on which we are filing a BLA. Patients receiving this treatment have continued to show improvement in their neurodevelopmental skill acquisition up to four years, and we recently observed discontinuation standard-of-care intravenous enzyme therapy.
Our recent milestones demonstrate how our new plan is supporting the acceleration in the development of gene therapies and the expansion of value for our shareholders. And today, we're providing some new guidance, as I mentioned, on near-term milestones for Duchenne and our treatment for wet AMD and diabetic retinopathy using in-office delivery.
Next week, we have plans to share new Duchenne trial update at the Muscular Dystrophy Association Conference being held in Orlando, Florida. Also, we expect to share new program and data updates for the Phase II ALTITUDE and AVA trials in Q2 in mid-2024, respectively.
Overall, we're absolutely thrilled about our status and the progress the company has made and with the way things have started off in 2024. I'm going to circle back in a bit and talk more about next steps for us. But for now, I'm going to turn it over to Steve, so he can do a deeper dive on the review of the clinical progress for our prioritized programs.
Stephen Pakola
Thank you, Ken. I'll begin with 314, which is being developed in collaboration with AbbVie to treat wet AMD and diabetic retinopathy via subretinal and suprachoroidal routes of administration. 314 utilizes the NAV AAV8 vector to deliver a gene encoding as therapeutic antibody fragment to inhibit VEGF.
The anti-VEGF market opportunity is poised to grow significantly as the population ages. 314 for the treatment of wet AMD via subretinal delivery is being evaluated in two ongoing pivotal trials, ATMOSPHERE and ASCENT, which are expected to enroll a total of 1,200 patients in the US, Europe, and Japan, and we anticipate global regulatory submissions in late 2025 through the first half of 2026.
In addition to our Phase II pharmacodynamic study that is evaluating the same dose levels being used in the two pivotal trials, we also have two ongoing Phase II trials that fall under our collaboration with AbbVie assessing in-office suprachoroidal delivery of 314 for the treatment of wet AMD in AV8 setting, and diabetic retinopathy, or DR, in the ALTITUDE study. AV8 is an active control, dose-escalation trial evaluating 314 for the treatment of wet AMD.
In January, we presented full six-month results from cohort 5 and 6 at the Hawaiian Eye Meeting. Consistent with previous update, the data presented continue to support the safety profile of 314 and showed a meaningful reduction in anti-VEGF treatment burden. ALTITUDE is the observation controlled study of 314 suprachoroidal delivery for treatment of DR. We're very excited about the opportunity in DR, given the size of this market, which exceeds that of wet AMD, and because we believe this patient population could benefit the most from a potential onetime gene therapy.
In November, we presented one-year data from dose levels 1 and 2, showing 314 to be well tolerated with patients demonstrating clinically meaningful improvements in disease severity with reductions in vision threatening events. We look forward to providing additional updates on this program in the second quarter of this year.
Moving to RGX-202, a potential onetime gene therapy for the treatment of Duchenne. RGX-202 is a highly differentiated product designed to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-terminal, or CT domain, found in naturally occurring dystrophin. RGX-202 is designed to support the delivery and targeted gene expression throughout skeletal and heart muscle using our NAV AAV8 vector and a well-characterized muscle specific promoter.
Our AAV Capsid also represents an alternative for boys who may not be eligible for other AAV-mediated microdystrophin therapies due to age or presence of preexisting neutralizing antibodies. In February, we presented exciting interim data from the Phase I/II AFFINITY Duchenne trial, demonstrating that RGX-202 continue to be well tolerated with no drug-related serious adverse events in five patients at both dose levels. All three patients at dose level 1 showed robust just RGX-202 microdystrophin expression and reduction from baseline in serum creatinine kinase, or CK levels, supporting evidence of clinical improvement.
RGX-202 microdystrophin expression from the third patient at dose level 1 was measured to be 83.4% compared to normal control at three months, the highest expression seen thus far. Importantly, we have seen RGX-202 activity in every patient and across a broad age group of both younger and older boys.
Coming up next week at the MDA Conference, we're excited to share new program and data updates from the Phase I/II Duchenne trial. We also look forward to sharing additional strength and functional assessment data later this year. Also, in February at the WORLDSymposium, we announced that the CAMPSIITE pivotal trial of RGX-121 for the treatment of MPS II met its primary endpoint with high statistical significance.
Patients treated with RGX-121 achieved decreased cerebrospinal fluid, CSF, levels of D2S6, a key biomarker of brain disease activity, to below maximum attenuated disease levels. We remain on track to file a BLA in 2024 under the accelerated approval pathway using CSF D2S6 as a surrogate endpoint reasonably likely to predict clinical benefit.
To conclude, we have made significant progress with data updates and trial progression across all programs in our pipeline. Lastly, I'd like to thank the patients, families, clinicians, and patient advocacy representatives who have supported all of these programs. And with that, I'll turn the call over to Vit to review our financial guidance.
Vit Vasista
Thank you, Steve. Regenxbio ended the quarter and year end on December 31, 2023 with cash, cash equivalents, and marketable securities totaling $314 million, compared to $565 million as of December 31, 2022. The decrease was primarily driven by cash used to fund operating activities in 2023.
R&D expenses were $232 million for the year ended December 31, 2023, compared to $242 million in 2022. The decrease was primarily attributable to a clinical trial and manufacturing expenses for ABBV-RGX-314, resulting in the increasing development cost reimbursement from AbbVie under our eyecare collaboration.
We expect the balance in cash, cash equivalents, and marketable securities of $314 million as of December 31, 2023 to fund our operations into the second half of 2025. This cash runway guidance is based on the company's current operational plans and excludes the impact of any payments that may be received from AbbVie upon the achievement of development or commercial milestones under our 314 collaboration.
With that, I will turn the call back to Ken to provide final thoughts.
Kenneth Mills
Thanks, Vit. Thanks, Steve. 2024, our plans are intended to generate significant value for our shareholders as we ensure that resources are allocated to our most valuable product candidates and to accelerate the development of these candidates. As outlined here today and supported by the press release announcements, we're motivated to expand value by addressing important unmet need in patients. We plan to achieve this in our eyecare partnership with AbbVie using our potential one-time treatments by sustaining vision health long term and overcoming clinical challenges of managing retinal disease.
Our operational goals without AbbVie are directed at completing work and assessments needed to support initiation, pivotal trials for 314 using in-office suprachoroidal delivery, and completing enrollment of our ongoing pivotal trials for 314 using subretinal delivery, which underpins our filing strategy for global regulatory submission by the end of 2025 through the first half of 2026.
Initial efficacy data from the first patients treated with RGX-202 is enabling us to accelerate this program. Duchenne is a market where there's a large unmet need for new therapies, and that is capable of supporting multiple gene therapies. And we believe RGX-202 has a unique differentiating set of features that support its potential to be a best-in-class product. We're taking steps to initiate a pivotal trial for RGX-202 this year.
Our recent top-line pivotal data supports that we are meaningfully changing the course of disease in boys with MPS II by restoring they're missing gene function. Based on these data, were working to file a BLA as quickly as possible. By the end of this year, everything in our pipeline should be initiating pivotal stage, fully enrolled at pivotal stage, or under a filed BLA. As a result of these recent updates and upcoming near-term milestones and milestones throughout 2024 announced today, we believe Regenxbio is well positioned for success this year and in the long term.
So thanks, everybody, for your time today. We hope that you share our enthusiasm about these recent updates, about the impact that our treatments and treatment candidates are having on patients. We also ask that you join us later this week in honoring Rare Disease Day.
With that, I will turn the call over to questions, operator.
Question and Answer Session
Operator
(Operator Instructions) Gena Wang, Barclays.
Gena Wang
Thank you for taking my questions. So congrats on the clinical progress here. So regarding the data update for both 202 and 314, one is next week and the other two is in later '24. So could you please lay out the additional data points that we will be able to see?
Kenneth Mills
Yeah. Thanks, Gena. Where not able to give that level of fidelity here today. With respect to the MDA Conference next week, we plan to have new data and updates about the program. And we're also under an embargo status with respect to the conference. So there is currently scheduled, though, a investigator presentation at the conference next week and also some posters that we have submitted previously as part of anticipated updates. And now, we're able to give more clarity that there will actually be new updates next week on 202.
With respect to 314 suprachoroidal, we're just continuing to share the data and the progress that we see happening with both wet AMD and diabetic retinopathy. We, just a few weeks ago, about a month ago, made the Hawaiian Eye update. And at the end of last year, we had the diabetic retinopathy suprachoroidal update. So more time has gone by, more work by the program teams. So there's going to be updates that include new data and new program updates we anticipate Q2 and mid-2024 with respect to suprachoroidal.
Operator
Vikram Purohit, Morgan Stanley.
Gospel Enyindah-Asonye
Hi, everyone. This as Gospel on for Vikram. We have one question for the 202 program. Since the last update, do you have any updated commentary on the baseline characteristic, patient characteristic for patient 3 that may have contributed to the higher level of microdystrophin expression reduction in CK levels for patient 1 and 2?
Kenneth Mills
Hi, Gospel. Thanks for the question. I think no new information since we updated last time in all the patients enrolled in the trial are meeting inclusion criteria, therefore, have backgrounds that are sufficiently similar. Obviously, we've got a wider age range here in terms of enrollment, 4 to 11. Then I think what people have been used to seeing from different data sets, this particular patient was 6.5 year old. And I think we were really enthusiastic about this being the largest increase in microdystrophin.
I think we attribute it to just some of the natural heterogeneity that can exist in the progression of the disease. And we certainly see this at the high end of the range of expression in terms of things that have been reported in general, including by other sponsors.
But I think it really, for us, reflects the robustness of the treatment. And we're going to be excited as we get into the dose level 2 to be able to continue to reinforce that. RGX-202 is a highly expressive and also contributes meaningfully to hopefully improvement in these boys.
Gospel Enyindah-Asonye
Thank you very much.
Operator
Alec Stranahan, Bank of America.
Alec Stranahan
Hey, guys, thanks for taking our questions. Just two from me. First on 314, we've obviously seen an increasing focus recently on other companies developing gene therapies for wet AMD. But obviously, you guys are still furthest ahead.
Maybe thinking beyond in approval, and I realize there's a lot of uncertainty to get to that point. But assuming 314 gets approved, what kind of competitive moat do you see being formed? IS this is a scale advantage having AbbVie as your launch partner? Wealth of data from the pivotal program, or maybe something specific to 314 itself? Any thoughts here would be great, and then I've got a follow up.
Kenneth Mills
Yeah, maybe all of the above, Alec. I think the real emphasis for us with 314 on both in terms of how far along we are in development and partnership with AbbVie and the investment that's being made in its development, particularly on a long-term outcome side, we have evidence of sustaining vision in patients and vision health long term out to four years.
And with that, we've even seen improvement in vision in some patients at three years and beyond to four years from a single injection, and that is with more than overcoming. That is with patients who have never needed an injection since they received RGX-314 in some circumstances. So that addresses the overcoming the day-to-day challenges that physicians and patients have with respect to managing retinal disease.
I think that that evidence of durability and that focus on vision is going to be incredibly important in clinical and commercial setting. Steve, I don't know if you want to comment about how you're thinking about that with the medical teams and how that translates.
Stephen Pakola
Yeah. I think the durability, as you mentioned, and certainly the opportunity to have this big of a database of patients and patient exposures combined with the durability that we can, show when you throw in the VA stability and even improvement in the setting of a dramatic reduction in treatment burden, that's really unparalleled compared to any of the competitors out there when you think of the combination of durability reduction and treatment burden with the VA finding.
So our investigators repeat this over and over again when they refer to the kind of results that we've seen to date.
Kenneth Mills
And as these partnership and thoughtfulness and views that have come to bear on thinking about how to influence clinical development, clinical development decisions, and the positioning of things late stages, we completed enrollment in pivotal trials for ATMOSPHERE and ASCENT , specially ex-US, have been phenomenal. I mean, they're obviously a great global partner with a global footprint and unbelievable engine for really tuning into the patient, and in this case, the retinal specialist experience to reinforce what they need some. But I really believe it's about long-term vision health, and that's the differentiation that we see with RGX-314.
Alec Stranahan
Okay, great. That's helpful. And then maybe one quick one just on the cash runway. Some big events anticipate that could trigger milestones from AbbVie over the next 12 to 18 months, let's say. But are there any other levers you guys can pull and push this past second half of '25 if needed? Or are you pretty comfortable with it setup in regards to the runway? Thanks.
Stephen Pakola
I think we said after we introduced our updated strategic plan last year and the cost reductions that we were, as a company and our Board of Directors very focused on enhancing value for shareholders, and that that meant focusing on very high potential opportunities with differentiation, commercial opportunities that were meaningful. It involve some hard choices.
And some of those choices were reduction in burden. We've been seeing early on this year that we've been achieving those goals and continue to be on track to not only maintain that guidance, but continue to be confident in it. And I think with respect to, yeah, that basket of milestones, having just reported the top-line data for RGX-121 pivotal and seeing that, being able to share that for the first time and some of the other observations like the reduction and changes in enzyme replacement therapy continuation, we're feeling really confident about the BLA filing, really working as quickly as possible to get that on track. Of course, with the BLA approval, we've expected that we could be eligible for a PRV.
And talking today about the notion of updated data and updated progress on suprachoroidal positions us for the ability to achieve some of those additional milestones as well as part of the AbbVie partnership. So I just think a few months removed from the updated strategic plan and the focus. We're really enthusiastic about the momentum that we have, with the science, and with this plan right now. I think the capital is in a good place.
Alec Stranahan
Thank you.
Operator
Ellie Merle, UBS.
Hi, this is Sarah on for Ellie. Thanks so much for taking out question. I guess two quick ones from us. Can you talk about your most recent thoughts on expectations into initial strength and functional data from 202 later this year? And then also, can you remind us is longer-term data from the supercuroidal 314 program gating to starting Phase III or potentially we could start a Phase III before we see that data? Thanks so much.
Kenneth Mills
Thanks, Sarah. With respect to strength and motor function data over the course of 2024, we've guided that we expect to be able to achieve that and share that for both dose level 1 and dose level 2. I think with the microdystrophin expression that we've been seeing to date with dose level 1, we continue to be really enthusiastic about the fact that there's an approval of endpoint that has been supported by the FDA. It's therefore been labeled as a surrogate. That's reasonably likely to predict clinical benefit, and the clinical benefit that we're all looking for here is improvement in strength and motor function in these boys and daily activity things as well as routinized assessments for those.
So, no, I think we're on track. The guidance that we're giving us still to progress through with microdystrophin updates additional data about how we're going be making sort of pivotal dose decision, which is really going to be weighted towards microdystrophin data and safety data.
And then by the second half of the year, as we've migrated towards our final plan for initiation of pivotal trials, I think then that strength and motor function data will be more mature and will be something that really will start to cross-communicate not only with pivotal plan, because that's really going to be an accelerated approval strategy based on microdystrophin, but it'll start to set up the conversation about confirmatory evidence as well.
So I think everything's on track as we've expected it it could be by now. And again, we're going to have another update just announced today with some new data at the Muscular Dystrophy Association Conference next week to continue to let this story breathe throughout 2024. Stephen, on the second question.
Stephen Pakola
Yeah. So thanks, Sarah. So you mentioned long-term data, how much do we need in suprachoroidal before we're thinking about Phase III. I think it's important to mention that, for example, with diabetic retinopathy, we know what is an acceptable pivotal endpoint and its use of the validated DRSS scale. And we know that that's had a one year time point. And we now, as Ken mentioned, we fortunately -- late last year were able to present one-year data from dose levels 1 and 2 where they both were well tolerated.
And we were seeing not only proof of concept, but exactly what we want to see in terms of improvement on diabetic retinopathy severity and a dramatic reduction in vision threatening events. So that really puts us in the AbbVie and a good position as far as assessing the potential to move into later-stage development. But we're not in a position to give any anymore details or any kind of timeline on it other than to just give you that sense of how we can assess this data both from a safety and efficacy standpoint.
Great. Thanks, guys.
Operator
Annabel Samimy, Stifel.
Annabel Samimy
Hi, thanks for taking my question. Just to follow up on the DMD program in terms of the selection between dose 1 and 2 for moving into the Phase III. You just mentioned microdystrophin levels and safety data. But I guess to get a little bit more granular, is there a level you're aiming for as far as microdystrophin expression that correlates better with potential functional benefit that you're looking for? Or are you just trying to determine whether you can probably reach a broader swath of the population with as high dystrophin levels as possible as long as that safety stays intact? That's my first question.
Kenneth Mills
Yes. It's a great question, Annabel. I think we're drawing on several different resources at this point in terms of how we're thinking about pivotal dose determination. And we've guided to the fact that that's a mid-year decision for us. First, we're clearly impacted by microdystrophin levels that we've seen at dose level 1. And we're excited. I mean, we're seeing signal in a wide range of boys, in all boys age range wise.
And we're seeing differences, but I think that they're -- in some cases, they're explainable. In older kids, I think there's some evidence of additional progression in disease. So we have over 10 year old had a lower level of microdystrophin. And in that particular case, that may be something where a dose level 2 will be in important in the other boys, the four year old and the six year old to date.
We're seeing things that are well within the range of -- the product that's already approved on the basis of accelerated approval and evidence that in other cases with other sponsors, they've seen forms of improvements in boys in terms of strength in motor function at these types of levels.
So again, the enthusiasm at dose level 1 is very high. And we look at our preclinical data and we brought this forward last year as well. We reran some preclinical studies directly comparing dose level 1 and dose level 2 in mdx mice. And we see separation. We see better results with dose level 2. And so to the extent that that data directs us as well is dose level 2 is safe, which it has been reported to date and continues in our view to be.
It's going to be hard to want to step away from that because I think we're just naturally going to expect more is going to get us more expression. More expression is going to get us improvement in function. So I think we'll keep playing that out in the first evidence of dose level 2 expression. And other observations are going to be important contributions to that. And that's why on starting next week and into the middle of the year, we have expectations that we'll be getting more data to sort of help shape that entire decision.
Annabel Samimy
Okay. And is there any chance that you move forward with two doses, or is that not something that's done in gene therapy?
Kenneth Mills
No. it's not something that I think we -- of course, we've done that in ATMOSPHERE, in ASCENT, in retin, as well as anyone that can be more commonplace and for masking purposes and other reasons, probably good reasons to do that and some of the retina settings. But for rare diseases and with respect to MPS II as well as Duchenne, I think we've been focused on single-dose trials with the doses that can provide the greatest evidence of not only the gene turning on the proteins themselves expressing, but any phases of development, the strongest evidence of both safety and functional benefit.
And so it will be 2 or 1. And the preclinical evidence says it's 2, but the clinical evidence right now says 1 is really good. So I find, for us, that's actually not dissimilar to things we observed with 121 where we were seeing expression dose escalated, ultimately took the highest dose into pivotal with that was a safe dose. And you look at what we achieved with respect to the pivotal result there, I think we're following a similar playbook here.
Annabel Samimy
Great. Thanks very much. Appreciate the color.
Operator
Brian Skorney, Baird.
Hey, guys, this is Charlie on for Brian. I want to ask a question about 121. I was wondering, looking at the difference between the patients who are less or greater than 2 standard deviations below the mean age equivalent skills, how do you think about the difficulty of showing gain of skills in those patients in terms of -- could this affect the label? And will this affect your commercial plan? Do you expect those patients to be treated as well? It would just be great to get some color on that. Thanks.
Kenneth Mills
Yeah. It's also a great question because I think we brought forward this really interesting data in terms of stratification. We had a call today. We've had calls recently with rare disease families and parents and investigators and partners. And I think one way to answer that, Charlie, is disease stabilization is improvement for families and for children. And I think that's -- not all kids, depending on progression of disease, age, what their journey is or diagnosis and when they present, right now, in Hunter and in Duchenne, are going to be able to be finding access to things like gene therapy and other care at a point in time where you can expect to see the type of improvement that we're seeing in the kids that are within 2 standard deviations of the mean. And that's usually that's each age correlated, but we've decided to step out a little bit under the spotlight of just saying it's about the age and getting kids younger. I mean, that's certainly true, but it's not exclusively it. It is about progression as well.
When it comes to thinking about the commercial benefit -- and the clinical benefit in the commercial setting, rather, I have to say, we've shown the [baleys], and we're very transparent about what we're seeing in terms of the different functional indices in assessments that we do clinically and that there can be differences.
What we sometimes talk about less, though, I think is going to be a part of the conversation with payers and in the commercial setting, is when we are seeing stabilization, what impact is that having a home? What impact is that having on family? What impact is that having on sleep patterns, on toileting, on engagement with the boys among their families? And those things are not to be discounted in any way, shape, or form. They are more caregiver and patient-reported outcomes, different than the analysis that we do in these structured forms of evaluating behavior and neurodevelopment.
So I think we've also -- even in this program for 121, had a trial publicly available that we dose kids over the age of five that are much older than any place that you would even expect, even potentially see the type of stabilization that we've shown in the setting so far. And there are things to take away from that are valuable for patients and families.
So overall, I think getting kids earlier in the progression of the disease and younger is going to result in some of, I think, the strongest outcomes when it comes to the literal interpretation of neurological development, behavioral development, fine motor skills and so forth. But there's a lot of kids I think that also can benefit from gene therapy on the basis of that stabilization comment.
And those are also some of the kids that may benefit from the discontinuation of enzyme replacement therapy, which while it may not be something that is part of the label initially, I think it's going to creep into the clinical and commercial consciousness over time. So I feel like 121 is a very strong clinical data set to support high unmet need across a lot of boys with Hunter.
Yeah, definitely. Yeah, the data is great. So thank you for providing that extra color.
Operator
Danielle Brill, Raymond James.
Hey, guys, it's Alex on for Danielle. Just a big picture question again on DMD. Curious to know how you interpreted some of the regulatory comments made last week at the FDA biomarker workshop about needing to think about subsequent therapies and impact on patients potentially not being able to get a better gene therapy in the future. Might that imply that limited label expansion may be limited to just for four to seven years old, considering that's the population that they studied in their placebo-controlled trial?
Kenneth Mills
Almost feels like a loaded question. I think that we have -- look, we are in a mode right now with 202 where we're just beginning to see what the potential is here. And I think with additional updates and additional data, I think then we can really feel like we can move ourselves into the conversation.
We're there. We have differentiated biology. We have something that I think is an opportunity for variety of different stakeholders to pause and think about what's the innovation of adding the C-terminal domain to NAV therapeutic can mean, what can I mean from a surrogate endpoint perspective but also from the longer-term outcomes perspective.
And I think we appreciate the complexity that NAV development and in the regulation AAV, you're setting things up as precedence in ways that I think are important and need to continue to support innovation. And that's what we hear, and that's what we see from the approaches that have been taken by the agency in the case of -- a lot of work that's going on in gene therapy. So I think that -- yes, we think that innovation continues to be important.
We think that when we're showing data in older boys, for instance, that we think that, that evidence and that information is useful to contribute to conversations within the community and all stakeholders, including regulators about how to help steer our development plan in our approach and things that may come after us. That's further improvements.
So we like to hear that those thoughts are happening and that those conversations are happening, and we feel it as well in our direct interactions.
Danielle Brill
Fair enough. Thanks for the call.
Operator
Luca Issi, RBC Capital Markets.
Luca Issi
Hello, great. Thanks for taking our question. This is Lisa on for Luca. Just a couple on MPS II. So first, a question on your regulatory strategy. I know you have reiterated that biomarker reduction at four months is sufficient for accelerated approval. However, we know so now we have to run a head-to-head trial versus ERT as the Phase II/III study, which is five times bigger and six times longer than your CAMPSITE Phase II.
Is there any chance that the FDA opts to hold RGX-121 to the same standard as Denali? And I have a follow-up. Thanks.
Kenneth Mills
Hi, Lisa. Thanks for the question. The target product profile for RGX-121 is specifically focused on addressing the neurological complications of MPS II in kids with no neuronopathic mutations. And that's where we focused all of our clinical development that has led to the selection of a pivotal dose and execution of the pivotal phase of the CAMPSITE trial.
And in that case, it means we've enrolled the demographic of kids that are pretty young, in some cases, just months old, and not always as progressed in the disease, but sometimes they have siblings or have known neuronopathic genotypes that are basically certainty of their progression in their characterization.
And that's the label we're looking for. We're looking for the treatment that comes forward with this accelerated approval exercise to be something that is delivered on top of the [IVL appraised] to address the high unmet need for the kids with neuronopathic mutations, while they still have benefits from things like IVL appraised, they're dying from the brain disease. And we're looking to address that and reconstitute function at the gene level to not only look to achieve to save them from dying, but also to get them back on the path of either normal growth and development or stabilized growth and development.
And I think FDA has expressed with us and publicly a real openness to the use of really well characterized biochemical marker, which is the natural substrate of the enzyme that's deficient in boys with Hunter syndrome. And just last week, we were at a meeting, including Denali and Ultragenyx and others, lobbying for the use of that biomarker in the setting of accelerated approval. And I saw a real meaningful advancements and conversation occurring there. And we're all working together on this, I should add.
I'm pulling for Denali, and I'm pulling for treatments for other MPS, and I think in the same way that I see from the constituents at those places pulling for us and pulling for RGX-121. So if we don't control what the FDA does across all the different sponsored programs, I think all we can communicate is that we've tried to be very focused on what part of the disease and MPS II we think 121 can show the most benefit, design a therapeutic candidate and a set of trials to achieve that.
And with feedback all along, I think we're in an excellent position with our approach to file a BLA as quickly as possible here. So there are differences between the different types of approaches and different products. They have different part product profiles, and they're looking to achieve different things.
But when it comes to things like using a biomarker to support accelerated approval, when it comes to using that biomarker to assess it as a surrogate endpoint, we're on the same page with a lot of other people. And we're really encouraged about where our program's going and hope that that also is, frankly, something that's an observational change for other programs as well.
Luca Issi
Got it, got it. Super helpful. And just a follow up from CAMPSITE. Do you have any plans to share additional biomarker data such as systemic reduction of GAGs or NFL? Any color would be helpful. Thanks.
Kenneth Mills
We don't have any specific guidance right now on MPS II other than filing of the BLA. And I think that's really where all of the focus, resource, energy, effort, and having achieved the primary endpoint based on the trial design, that's where we are.
I think we -- maybe we get into the second half of the year. And as we started to talk more about post-filing, what's happening with respect to the commercial setting, and what additional data may be useful to frame out things, that get described are defined in label or in terms of things that are helpful, that may be something we focus on. But right now, the focus of the team internally is completing the modules, completing the follow-up of all patients on safety to support the BLA filing the second half of this year.
Luca Issi
Got it. Thank you so much.
Operator
Mani Foroohar, Leerink Partners.
Mani Foroohar
Hey, guys. Thanks for taking my question. Obviously, there's been a lot of big name on the pipeline. A quick clarification. You guys laid on your financial guidance that you've got cash runway, it looks like to the back half of '25, but you do delineate in the press release a number of NAV technology platform license fees that you define as having meaningful milestone throughout 2024. I think you call out Ultragenyx, Rocket, Novartis, specifically, if memory serves.
Could you walk through this year and highlight individual events that would result in cash flows coming to you guys? Or are you changing the accounting treatment and value carried on your financial statements for any of the licensee programs? Just trying to understand what that means for you guys financially or from an accounting basis.
Kenneth Mills
I think the things we pointed most to money in terms of potential impact on balance sheet are the milestones certainly that are associated with the transition of suprachoroidal into pivotal phase with AbbVie. Those have been the major priorities, and then the potential to achieve a pediatric review voucher upon the approval of RGX-121.
And I think our guidance on all of those things have been -- they're event-driven, obviously, but there are things that we see the potential for them to occur over the course of our existing execution timeline. And those are hundreds of millions of dollars individual events. When we start to look at the section on the press release in the history of the company around our NAV technology platform licensees, it's a great and interesting question.
I mean, obviously, the impact of Novartis as we continue to report quarterly sales and annual sales, as to this point, not really changed our balance sheet since we did the monetization of the Zolgensma royalty, and we continue to see the impact of that being limited over the course of the next year, certainly into 2025.
That might change. We're seeing some evidence of regulatory progress, for instance, on the interest equal Zolgensma approach, which could change the labeling or change the product availability of the AAV9 expressing SMN. But we're not planning to include any additional discussion or guidance in terms of thoughts about that impact in the near term.
When it comes to Rocket and Ultragenyx, I think we've identified that they have two or three programs collectively in pivotal phase, and that the approval of those products, the reporting out of pivotal data may give us a bit more evidence and confidence to talk about the likelihood of achieving milestones for product approvals.
And so, again, those are event-driven things that could occur as they've guided over the course of this year or even into 2025. So I think that's how we've been thinking about identifying and sort of focusing on the NAV technology platform licensees and the drivers of value. I don't think that our licenses and maybe the interest equal Zolgensma could be something that would be an exception to this.
But I don't think that those types of milestones are necessarily at the same level as a PRV or the types of milestones that combined $0.5 billion in milestones associated with AbbVie partnership suprachoroidal progress would be in the same range. They might be, though, I don't know, 5 to 10 times less than some of those things on a generalized basis when you look at the historical benefit of our licensee milestones. Is that helpful?
Mani Foroohar
No, that's really helpful. Thank you.
Kenneth Mills
Yeah, good question.
Operator
Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.
