Chris Cline: And Liisa, just on the gross to nets, we’ve been pleased with how we’ve seen things meet our expectations of having a mid- to high teens gross to net. The other thing that I would say is for 1Q with the rest of the year, we may see that be a little bit higher as we have some of our other products in the past. But overall for the year, we would expect it to remain in that mid- to high teens level.
Liisa Bayko: Okay. And then can you comment at all on like how many patients were on kind of exiting 2023 on FILSPARI?
Eric Dube: So we’ve not provided guidance for any KPIs on a number of treated patients. I think Peter can talk about directionally what we were seeing as we ended the year. But Liisa, we’re going to continue to provide updates on PSFs on payer coverage and on revenue at this point in the launch. Peter, you want to provide anything further to this question?
Peter Heerma: I think that’s right. As I mentioned earlier, I think we’re making robust progress on all the fundamentals, including the pull-through getting patients on base product. I think the process is well within benchmarks which you would expect from rare disease products. And so I think we will see that continuation and it will be reflected by revenue as well to Eric’s point.
Operator: Our next question is going to come from Vamil Divan from Guggenheim.
Vamil Divan: Great. Maybe just a couple of follow-ups on the payer side. So I think, Peter, I think you mentioned your prepared remarks that the payers are — they’re sort of acting generally consistent with the label in terms of the patients that they’re reimbursing therapy for. I’m curious if maybe you can just give a little more detail there in terms of when they’re deviating from the label sort of what issues, if any, are they sort of raising? And then the second question I have is more around the full approval, assuming you get that sort of later in this year, would you expect sort of a sort of immediate change in sort of payer behavior on that? Or is that something we’ll have to wait until sort of the 2024 — 2025 cycle starts up in terms of formulary status or authorizations.
Eric Dube: All right. Peter, I’ll hand those over to you.
Peter Heerma: Yes. With regards to authorization criteria. I mean there’s always certain effects that the payer is expecting to see — and so I think where we are is that especially in the beginning when we got the label and the label was kind of safe on patients with rapid progression of disease with regards to proteinuria states like generally 1.5. When we are seeing that players in most of the authorization criteria refer to the label but also refer to the clinical guidelines and that has lower proteinuria targets. So that allows for a broader use. And that’s why to my earlier point in the call with a further lowering of the proteinuria targets within the legal lines [ph], a company is like a broad label fulfills powering that would allow them also for a broader patient population that is eligible for paid products.
Eric Dube: And then, Peter, what is your comment on the question around full approval and how payers will respond with full approval and how quickly they might be able to review.
Peter Heerma: Yes. So I think it speaks a little bit to what I said with a further lowering of proteinuria target and then also a broader label, whether it’s no restriction in proteinuria that authorization criteria on a threshold of proteinuria may disappear. And so that allows for a broader patient population. I think that’s one aspect. I think another aspect is — and I think your question may have been referring to like the evolving competitive landscape as well with new competition coming in. I think the lead time that we have and the strong base that we have in formularies provides a very strong position, especially since we have like the highest standard for study design. I mean this is the only study that has active comparator which is basically the gold standards how a payer is evaluating new products. So I think we are in a strong position with regards to lead time as well as study deciding how payers are evaluating that evolving landscape.
Operator: And our next question is going to come from Alex Thompson from Stifel.
Alex Thompson: I want to pivot a little bit to pay the bad news here. Maybe could you talk a little bit about the HARMONY study through the expectations around enrolling 70 patients or at least up to 70 patients based on your experience with the Phase I/II, how well identified are these patients? If this is a 12-week primary endpoint of the top line is the 2026 readout conservative at this point? Or how are you thinking about that?
Eric Dube: Alex, thanks so much for the question and also for the focus on the pegtibatinase program. Jula, I’ll turn that one over to you.
Jula Inrig: So thanks. We think this is an exciting trial design that focuses on changes in total home 15, not just at 6 to 12 weeks but also looking at durability of effect. So it is a 24-week study and then patients roll over to our open label which is able to look at diet liberalization. And to your point, we are looking to recruit 70 patients from more sites than we did for COMPOSE. It’s about 50 sites overall which will give us top line data in 2026. And while we have started the trial and we do have a list of patients who are excited to participate. We are intentionally moderating our enrollment initially to ensure we have a good experience for the sites and patients and also proper training at some of these sites to — some of which are research naive and then also to ensure our CMC scale up to support the full study as well as commercialization.
Eric Dube: So I think perhaps if you can comment on the enrollment period before for screening that it helps explain why the time line may be a bit longer than what people would typically say for this type of trial.
Jula Inrig: Yes. So because it is a 6-month trial, plus we have a 10-week run-in period where patients get screened to make sure they qualify as well as standardize their diet and that’s really to try and optimize our chance of success that patients have understand the trial that they need to keep their diet table which clearly is going to impact your endpoint. We want to maximize our chance for success at the end. So it’s a bit longer than what you first stated.
Eric Dube: Yes. And we’ll certainly look to move swiftly on this but we — for all of the reasons that you’ve explained, we’ve been very thoughtful around the time lines that we’ve put out there. Alex, the only other thing that I would mention that we — that gives us confidence in the enrollment is that as we see increased awareness within this community, there are more and more patients that are being identified and we would absolutely expect that there will be a growth in the number of patients identified, diagnosed in the overall market growth. So this is something that we believe will certainly be a tailwind for us with the HARMONY trial and even more so as we look to reach these patients once we have approval.
Alex Thompson: And I guess, how many patients do you feel like you need to enroll to feel confident in powering if it’s not 70.
Eric Dube: Bill, why don’t you talk about the powering but I can say we absolutely are confident in finding these patients. I think we’ve been able to help in thinking through where these patients are, with sites, et cetera. So I think Jula’s team has done a really great job of ensuring how we can enable success in the HARMONY trial. And I think, Bill, you can talk about a high level of the powering.
William Rote: Yes. No, certainly and I appreciate the question. We’re very confident in the powering of the study. And recall in Jula’s initial remarks, she mentioned the 67% reduction in total homocystine that was observed in Phase II. So with that level of efficacy, even with a significant diminution in the treatment effect or a reduction in the overall total sample size which we don’t anticipate. We certainly are in a good place to still achieve the endpoint. So I’m confident that we’ll get there.
Eric Dube: Jenny, can we move to the next question, please?
Operator: Yes, we have Mohit Bansal [ph]. Can you hear me?
Unidentified Analyst: Just wanted to understand. I mean I know you don’t provide the patient count. But if I look at the average number of patient forms, coming from second quarter to third quarter and then third quarter to fourth quarter, it seems like there’s a 57% increase but then there’s a substantial increase in revenue. So is this because you are converting a lot more of those patient form into paid patients? Or is there a stocking in part involved here? Can you help us understand that? And then last — second question is on the price increase, I think you took a price increase in January, should we expect some benefit in 2024 due to that price increase?
Eric Dube: Okay. Thanks so much for the question. Peter, I will turn that over to you.
Peter Heerma: Yes. So thanks Mohit for that question. So as I mentioned, like one of the core fundamentals is making sure that patient forms transition ultimately to patients on products and in particular bases on paid products or you continue to increase the revenue. And I think what you saw in this quarter is that we made robust progress in particular, also in the pocket of patients that we described in the earlier quarter that required some additional handholding and education with regards to the REMS loss I think — as I mentioned, like the patient REMS certification within the first 14 days has increased quite substantially and that allow patients to go through the process and get to base product more quickly. So good progress there.
To Eric’s earlier point, we don’t provide further details on how many patients we have on product. But I think that transition from patients to our form ultimately get paid product, we made significant progress. On the second question with regards to price and price increase, indeed, we had a price increase in the beginning of the year. Now that we have the confirmatory data and you see that proteinuria reduction — the robust proteinuria reduction provides longer-term eGFR and getting preservation as well. So we thought it was justified to have a price increase for this year.
Eric Dube: And maybe just one final thing, Mohit, for your question on inventory. That has been stable, so there has been no pattern of stocking. So I think Peter is absolutely right. We expected to see a greater inflection in revenue as our teams are able to help those patients through the process. You would imagine that, that is going to continue that trend this year with faster growth in revenues than perhaps what we see in patient start forms but we’ll certainly apprise you how we’re doing at the end of Q1.
Operator: And our next question is going to come from [indiscernible] from Citi.
Unidentified Analyst: I had one on FSGS. Just curious if there were any recent updates with regard to the work that I believe the FDA is doing in collaboration with you on defining some of the optimal endpoints for FSGS, whether there’s some variations of the eGFR slope endpoint that may be more appropriate based on some of the data cuts that you’re exploring? And then secondly, on the broader landscape in IgAN, just wondering, obviously, there’s been a lot of visibility around some of the newer mechanisms, anti-B-cell mechanisms. Wondering whether FILSPARI, given the position is the conditional therapy, may benefit from a combo study using the B-cell modulators on top of FILSPARI at a future point.
Eric Dube: Great. Thank you for the questions. And Jula, I will turn those over to you.
Jula Inrig: So thanks. As far as FSGS, we are continuing to do our processes with our data and external data sets, putting our trial into historical context. With regards to the FDA, this is a partnership with [indiscernible] which is a patient organization with academics and the FDA. And it’s called Parasol [ph]. There’s a website it’s public and it’s really to redefine the endpoints. And what they’ve recently announced is they’re really looking at alternative proteinuria-based endpoints to help enable the regulatory pathways for FSGS. We plan to reengage the FDA following their final analysis and decision on what those endpoints should be under this Parasol Group [ph] and they’re targeting ASN for that time line?. And then your second question is around some of the newer agents and how FILSPARI should be placed.
And I think it’s really going to be an exciting few years for IgA nephropathy patients in some of these new therapies most of which target different parts of the injury cascade contributing to IgAN and hopefully, they’ll become available outside the context of a clinical trial but we’re a few years away from that. But I would add that all additional immunomodulating agents are being used on top of standard of care foundational treatment. And that’s where FILSPARI plays a foundational role because it targets the injury in the kidney and the response to the [indiscernible] deposition and protects against further damage. And really, we’re really aligned with the KOLs. You need to target 2 things ongoing damage in the kidney with foundational treatment.
