So it’s really extraordinarily high levels. If you were going to see the similar kind of effect in terms of negative impact on the threat, you would have seen it by now in our opinion. But we’ll continue to monitor it. And if we see that shift at all or as we go up in even higher doses, we encounter that, we’ll share it. I think at this level, given the PVR reductions that we’re seeing and assuming that they’re correlated with drug use, we’re really happy with the profile of this drug.
Operator: And your next question comes from the line of Graig Suvannavejh with Mizuho Securities.
Graig Suvannavejh: Congrats on the quarter. Two questions, please. Maybe I’ll ask a question actually on the earlier-stage pipeline. I just wanted to get an update maybe on your DMD program. I think the trial was supposed to start this year. It looks like maybe it’s not starting this year. So maybe you could just review kind of the ongoing activities there. And then with that in mind, I didn’t know if you had a view on Sarepta’s Phase III EMBARK data and whether that data will inform how you think about the program that you’re developing? And then my second question is really a financially oriented question. You’ve got cash well through the readout of ASPEN. And I just wanted to get a sense of assuming that you do get positive data, which I think we’re all hoping that you’ll see.
Can you give us a sense of how you’re thinking about any kind of next financing, what that might look like, whether you’re thinking about equity debt, a mix of both? Or is there another alternative financing solution that you’re considering?
William Lewis: So on the first question, when we think about our research pillar, so-called fourth pillar, as I was saying earlier today, like there are now more than 30 pre-IND programs in that effort. Underneath that umbrella for gene therapy, we have half a dozen that we’re pursuing at the moment. DMD is one of those, but they all sort of exemplify the same strategy that we have for this area, which is that we’re going to be bringing some really cutting-edge technology to try to advance and improve dramatically on the ability of these modalities to have impact on patients. In the case of DMD, in the first instance, that will involve intrathecal delivery. And so that has involved some back and forth with the agency to make sure that they’re comfortable with that technology being deployed in that way.
So that process is ongoing. I would say it’s very productive. But I’m not surprised that we’re going to be having this kind of dialogue with the agency because we’re bringing that. We intend to bring forward deimmunized capsids. We intend to manufacture them. And algae, we intend to do RNA End-Joining, which is multiple capsids creating longer length proteins. There’s a lot of stuff we’re bringing forward that is really going to be able, we think, to transform the way gene therapy is used and the impact that it has on patients. So I expect some puts and takes there. But overall, I would say that all of our programs and all the science behind them continues to get better. So as those programs advance, I think the benchmark we look for internally is when are they in Phase I/II because we know that’s when you all will start to pay more attention.
It’s not that the work isn’t important or that it isn’t significant. It’s just — it doesn’t have as much relevance to the investment community until it’s sort of inpatients. So we’ll continue to keep you updated as we make progress there. With regard to Sarepta, I’m not — we’ll be watching their data as will everybody else. I think we are hopeful that they’ll have success for the benefit of the patients. But we certainly will look at that data and learn whatever we can from it. Once again, we think that our intrathecal approach is going to have a significantly greater benefit to patients. And that’s based on the fact that the data that we shared with you in our Research Day suggest that to be the case. With regard to the cash position and what we’re doing in the future, I’ll turn that over to Sara.
Sara Bonstein: Sure. Yes, happy. Thanks for the question, Graig. And just a reminder, on the early stage, less than 20% of our investment is in that arena, obviously, very important, but can state-gate that investment pretty closely. So on cash, we feel really blessed to be in the position we are over $0.75 billion on the balance sheet as of the end of the quarter. been able to continue to unlock value here, continue to the stock — it’s a tough macro market, but we have been able to continue to outperform, which is great. As you said, we’ve been very clear. We are not funded through profitability. We will need to raise at some point in the future. But we — I feel very privileged that compared to many, we have a lot of different levers and have the ability to take — to be kind of thoughtful as we think about balance sheet augmentation and be able to do it in many different ways if and when we so choose to.
So where we are now, shareholder value over $0.75 billion and have a lot of optionality down the road.
Operator: And your next question comes from the line of Stephen Willey with Stifel.
Unidentified Analyst: This is [indiscernible] on for Steve. I hope everyone can hear me okay. Congrats on the data and quarter earnings. I have my question is mostly around TPIP data that you always released. So very first question that I want to start with is that could you guys please provide us with a little bit more clarity on the rationale regarding like why you need to stop dose titration at week 5. And would you expect an even greater proportion of patients to get to the top dose? And lastly, the question related to protocol amendment. So when do you expect this protocol amendment to be finalized? And is there any plan to communicate this protocol amendment finalization through a press release or something like that?
William Lewis: So the design of the study is sort of consistent with other studies in PAH and PH-ILD. I don’t think there’s any particular magic to the moment of cutoff for titration. All I would say is that the practice in the clinic is to get patients to as high a dose as you can. I think to get equivalency your — that’s just the reason for the structure. And I’m sure that in practice, physicians will take time to increase dose. And I do think that as you go up in dose, as long as there’s not an adverse event profile, you’re not going to — you should continue to see benefit. And the idea that you can go even higher is pretty exciting. With regard to the protocol amendment, what we press release when that’s accepted or not, I’m sure we’ll include it in our disclosure at some point, but I don’t expect a separate standalone press release.
I think that would just be something we’d convey in a quarterly call or some other medium. I will just add that I think the objective of cutting it off earlier is once you get to your max tolerated dose, you want to track what happens with patients at that highest dose. And so you want at least 11 weeks on the final dose that you titrate to. In practice, though, as I said, they’ll go higher, I’m sure, after 5 weeks.
Operator: And there are no further questions at this time. Will Lewis, I will now turn it back over to you.
William Lewis: Great. Thank you all for joining us on this morning’s call.
Operator: And this concludes today’s conference. You may now disconnect.
