Ken 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 known neuronopathic mutations. And that’s where we focused all of our clinical development. That has led to the selection of a pivotal dose and the execution of the pivotal phase of the CAMPSIITE trial. And in that case, it means we’ve enrolled a 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 neuropathic genotypes that are basically a certainty of their progression and 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 Elaprase to address the high unmet need for the kids who, with neuronopathic mutations, while they still have benefits from things like IV Elaprase, 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 what is a 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 real meaningful advancement 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’s. And I think in the same way that I see the constituents at those places pulling for us and pulling for RGX-121. So we don’t control what the FDA does across all the different sponsor programs. I think all we can communicate is that we’ve tried to be very focused on what part of the disease in MPS II, we think RGX-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, look, there are differences between the different types of approaches and different products, and they have different 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 is going and hope that that also is, frankly, something that’s an observational change for other programs as well.
Lisa Walter: Got it. Super helpful. And just a follow-up from CAMPSIITE. Do you have any plans to share additional biomarker data, such as systemic reduction of GAGs or NFL? Any color would be helpful. Thanks.
Ken 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 maybe we get into the second half of the year, and as we start to talk more about post filing, what’s happening with respect to the commercial setting and what additional data may be useful to sort of frame out things that get described or defined in label or in terms of things that are helpful. That may be something we focused 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.
Lisa Walter: Got it. Thanks so much.
Operator: Our next question will come from the line of Mani Foroohar with Leerink Partners.
Mani Foroohar: Hey guys, thanks for taking the question. Obviously there’s been a lot of digging in on the pipeline. A quick clarification. You guys laid out in your financial guidance that you’ve got cash runway. It looks like the back half of 2025, but you do delineate in the press release a number of NAV Technology Platform licensees that you define as having meaningful milestones throughout 2024. I think you call out Ultragenyx, Rocket, Novartis specifically with memory serves, could you walk through this year and highlight individual events that would result in cash flows coming to you guys or in you changing the accounting treatment and value carried on your financial statements for any of these licensee programs? Just trying to understand what that means for you guys financially or from an accounting basis.
Ken Mills: Yes. I think the things we’ve pointed most to Mani in terms of potential impact on balance sheet are the milestones certainly that are associated with the transition of suprachoroidalinto 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 of individual events. When we start to look at the section on the press release and 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 has 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 intrathecal 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 in our licenses and maybe the intrathecal 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, five 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.
Ken Mills: Yes. Good question.
Operator: Thank you. This concludes today’s conference call. Thank you for participating. You may now disconnect.
