BioCryst Pharmaceuticals (BCRX) Q4 2022 Earnings Call Transcript

BioCryst Pharmaceuticals (BCRX -2.56%)
Q4 2022 Earnings Call
Feb 21, 2023, 8:30 a.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good morning, and welcome to the BioCryst fourth-quarter 2022 earnings conference call. [Operator instructions] Please note this event is being recorded. I would now like to turn the conference over to John Bluth at BioCryst. Please go ahead.

John Bluth -- Senior Vice President, Investor Relations and Corporate Communications

Thanks, Andrea. Good morning, and welcome to BioCryst's fourth-quarter and year-end 2022 corporate update and financial results conference call. Today's press release and accompanying slides are available on our website. Participating with me today are CEO, Jon Stonehouse; CFO, Anthony Doyle; chief commercial officer, Charlie Gayer; and chief R&D officer, Dr.

Helen Thackray. Following our remarks, we'll answer your questions. Before we begin, please note that today's conference call will contain forward-looking statements, including those statements regarding future results, unaudited, and forward-looking financial information as well as the company's future performance and/or achievements. These statements are subject to known and unknown risks and uncertainties, which may cause our actual results, performance, or achievements to be materially different from any future results or performance expressed or implied in this presentation.

You should not place undue reliance on these forward-looking statements. For additional information, including a detailed discussion of our risk factors, please refer to the company's documents filed with the Securities and Exchange Commission, which can be accessed on our website. I'd now like to turn the call over to Jon Stonehouse.

Jon Stonehouse -- Chief Executive Officer

Thanks, John. 2022 was another outstanding year for ORLADEYO as we doubled sales in our second full year of launch on top of the fantastic start we had in the first year. It shouldn't be surprising given the excellent safety, efficacy, and once-daily oral profile. We are consistently hearing from patients that ORLADEYO is changing their lives.

As you will hear from Charlie, in the U.S., our prescriber base continues to grow both in breadth and depth. In addition, ORLADEYO is already commercially available to HAE patients in 15 countries around the world. The ability of ORLADEYO to deliver meaningful results for patients is driving the steady patient growth we are seeing quarter after quarter. And in 2023, we expect this strong steady demand to continue, leading to the global sales of no less than $320 million.

Our goal with this guidance is very simple, to be accurate. Accurate guidance has been our track record since launch because we're the only ones with access to the prescription data through our sole source specialty firms. With our sales performance in 2021 and 2022 and our guidance in 2023, you now have three data points to get a sense of the slope of the ORLADEYO launch. We are on a trajectory to achieve peak global sales of $1 billion.

And our IP for ORLADEYO extends out to 2039, so we expect to be at peak sales for many, many years. While our revenues continue to grow, we expect our operating expenses to be flat year-over-year as we have made and will continue to make thoughtful capital allocation decisions on our pipeline investment. This reduction in net cash use has strengthened our financial position, moved us closer to profitability. You will hear more detail on this from Anthony shortly.

Now I'll turn the call over to Charlie to review ORLADEYO performance in more detail. 

Charlie Gayer -- Chief Commercial Officer

Thanks, Jon. The base of patients treated with ORLADEYO in the United States continued to grow as expected in the fourth quarter as new patient starts and patient retention remain consistent with the trends we have seen over the last two years. The prescriber base expanded strongly again, and existing prescribers continue to add new prescriptions. New starts on ORLADEYO were also distributed evenly, with just over 50% coming from the top tier of healthcare providers who treat half of all HAE patients.

As we begin 2023, we have confidence that we will achieve no less than $320 million in global revenue this year. Our U.S. field team expansion is in place, and patient growth trends are on track. Our European growth is also gaining momentum, and we continue to lay the foundation for ORLADEYO expansion globally.

And this weekend, we will present more long-term clinical and real-world evidence at the Quad AI meeting, adding to the growing body of evidence showing how ORLADEYO can improve the lives of patients living with HAE. We have noted before that typical U.S. payer reauthorization dynamics for rare disease products like ORLADEYO will soften Q1 revenue growth as many patients shift temporarily to free products. What we are seeing so far this year tells us that ORLADEYO revenue is likely to be flat to slightly down compared to Q4, even as our patient base continues to grow.

We ended 2022 with a total number of patients on ORLADEYO that we expected, and the patient growth trends we see in the U.S. and around the world give us confidence not only in our 2023 trajectory, but also that ORLADEYO peak revenue will reach $1 billion. Helen, I'll turn the call over to you.

Helen Thackray -- Chief Research and Development Officer

Thanks, Charlie. Today, I'd like to provide some additional updates on the next step for BCX10013, our potential once-daily factor B inhibitor for complement data system. As we shared last month, initial data from our Phase I single-ascending dose and multiple-ascending dose trials in healthy volunteers showed rapid, sustained, and greater than 97% suppression of the alternative pathway of the complement system 24 hours following a single 110-milligram dose and BCX10013 has been safe and generally well-tolerated at all doses studied to date in the clinic. These data provide early support of the development of BCX10013 and believe this product has the potential to differentiate once-daily oral factor B inhibitor for multiple complement system.

The next key step in clinical development is dose-ranging work in patients with the goal of confirming optimal dosing pivotal study. Nonclinical program helps us to address the safe dosing range we can evaluate in humans. Recently, we have seen emerging dose-related observations early in an ongoing chronic nonclinical studies, which were not seen at the same time period in a separate already completed study. We need to understand the full picture of these differences as they complete the currently ongoing study.

At the meantime, as a result of these observations, pace at which we can evaluate higher doses in humans to assess efficacy will be slower, and we expect a related delay in the timeline. So in order to grasp toward clinical dose selection, we'll continue working to understand what we're seeing in the ongoing nonclinical programs, and we'll keep you posted on our progress. In addition to BCX10013, we are making progress with our research program to identify oral medicine direct with its other targets across the classical selection terminal pathways of the complement system, including C2, which is a critical upstream serine protease enzymes for activation of the classical and lectin pathways. As we reported in January, we have developed potent, selective molecules targeting C2, and these are currently in the adoption stage.

Our long-term goal is for multiple, novel, orally delivered product forward to treat many complement systems. Now I'll pass it to Anthony.

Anthony Doyle -- Chief Financial Officer

Thanks, Helen. You can find our detailed fourth-quarter and year-end financials in today's earnings press release, and I'd like to call your attention to a few items. Total revenue for the year came in at $271 million, over $250 million of which came from ORLADEYO in just its second year since launch, more than doubling net revenue from the prior year. Revenue for the fourth quarter was $79.5 million, of which $70.7 million came from net sales of ORLADEYO, with the remainder coming from sales of RAPIVAB, including the fulfillment of the last of our contract in government stockpile orders.

Operating expenses, not including noncash stock compensation for the quarter, were $110.6 million. This puts full-year opex of $374.6 million. The increase compared to prior guidance was driven by almost $10 million of accelerated costs related to closeout activities for the termination of 9930 and 9250 programs. After the end of the year, it was up $444 million.

Earlier in the year, we provided guidance for 2023 ORLADEYO revenue of no less than $320 million. For opex, we expect 2023 to be flat the prior year at around $375 million. We previously stated that 2023 R&D investment would be in line with prior year. We're now forecasting that R&D expenses will decrease year-over-year following the discontinuation of the 9930 and 9250 program and the delay in the 10013 clinical program that Helen described.

This will be offset by additional commercial investments that we're making both here in the U.S. and as we continue our international expansion. As our revenue and opex curves continue to converge, we expect net cash utilization in 2023 to decrease compared to 2022, even when factoring in debt and royalty servicing. The combination of our strong balance sheet, increasing revenue, and our disciplined approach to capital allocation puts us in an outstanding financial position with an ever-decreasing reliance on the capital markets for funding.

Now operator, we'll be happy to open up to Q&A. 

Questions & Answers:

Operator

[Operator instructions] Our first question comes from Jessica Fye of J.P. Morgan. Please go ahead. 

Jess Fye -- JPMorgan Chase and Company -- Analyst

Great. Good Morning, guys. Thanks for taking my questions. Two for me.

I guess, first, what else can you share with us about the dose-dependent finding with 10013? And second, maybe a nuance here, but if I recall at the healthcare conference, you indicated that 1Q revenue would be roughly flat with 4Q, I think now you're saying flat to slightly down. Does that just mean we should think of 4Q revenue as being even higher than it would have been otherwise? Or does that take a little bit of the buffer out of whatever might have been in your full-year guidance? Thank you. 

Jon Stonehouse -- Chief Executive Officer

Do you wanna take the first one? 

Helen Thackray -- Chief Research and Development Officer

Yeah. Sure. Good morning So we -- in the nonclinical findings, what we're saying is that we are seeing something at a time point that we did not set at a time point in our other studies. And the impact then is that we want to learn more about the safe branch exposure, and we need to understand the difference. 

Anthony Doyle -- Chief Financial Officer

And, Jess, as far as the Q4 and Q1 revenue, so this was not a Q4 being bigger than it should be. It's really based on what we're seeing out there with Q1 reauthorization. It's always a challenge every year. And what we're seeing is that this year, it's just -- this isn't an ORLADEYO-specific thing.

Just broadly, the reauthorization process is just more work than ever, and so that's why we think it could be a little bit down or flat to Q4. But patient growth trends are on track, and the -- no less than $320 million is very much on track. 

Jon Stonehouse -- Chief Executive Officer

Yeah. And that part is really important to remember, that patient numbers are going up each quarter. But the reason revenue was flat to slightly down is because we have more patients on free drug going to the reauthorization. 

Jess Fye -- JPMorgan Chase and Company -- Analyst

Great. Thank you.

Jon Stonehouse -- Chief Executive Officer

You're welcome.

Operator

The next question comes from Tazeen Ahmad of Bank of America. Please go ahead. 

Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst

Hi, guys. Good morning, and thank you for taking my questions. On ORLADEYO, Jon, I'm just wondering what do you think could change in order for sales to be above the minimum that you have just guided to for this year? So outside of negotiating with payers, where else would you see a potential for upside relative to how you're looking at the market right now? 

Jon Stonehouse -- Chief Executive Officer

Yeah. I think for right now, we believe $320 million is the number, and that's the number of people should put in their model. But in terms of what could be a tailwind, I think Charlie's team is more successful than we had planned around getting patients from free drug to paid drug. You've got this expansion -- mini expansion that they went through late last year.

Maybe that has more of an uptick on revenue as well. Those could be things that could be a lift. 

Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst

OK. Great. And then maybe one question on 10013. I think you have previously highlighted that there was no consolidation tox seen before in your pre-clin models.

Is that still the case? 

Helen Thackray -- Chief Research and Development Officer

Yes.

Jon Stonehouse -- Chief Executive Officer

Yeah, this is very different than the 99 -- your question is around 9930 in comparison to the 10013? Is that --

Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst

Yeah, yeah. 

Jon Stonehouse -- Chief Executive Officer

Yeah, yeah. This is very different from that. 

Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst

OK. Thank you.

Jon Stonehouse -- Chief Executive Officer

You're welcome. 

Operator

The next question comes from Chris Raymond of Piper Sandler. Please go ahead.

Chris Raymond -- Piper Sandler -- Analyst

Thanks. And if you don't mind me beating the dead horse here. It sounds like you guys don't wanna answer a ton of questions on exactly what you saw, but I guess I'll just ask on 10013. When would you be in a position to tell us exactly what you found? And what's the path forward and the next steps for when the issues will be resolved? And then on the C2 program, I know you described this as a program that's in development.

But can you maybe give a little bit more color maybe on the timeline pathway to be in the clinic on that program?

Jon Stonehouse -- Chief Executive Officer

Yeah, I'll take the second one. You can take that. Helen, you can take the first one. So what we said in January is the C2 programs in lead optimization.

And it's hard to predict when it will get into tox and Phase I studies, but it's just lead optimization now. Once we pick a lead, we'll go into tox and move forward from there, but we can't give timing on that right now. Then the first question is around?

Helen Thackray -- Chief Research and Development Officer

Yeah. So on 10013, what we're seeing is that we're seeing something that is different. We're seeing it at the same time point where we did see it before. What that means is that we need to learn more.

We need to learn more about that difference, and we need to learn more about the nature of what we're seeing. The goal here is to understand the safe range of exposures, and that's the point of the nonclinical work at this point. The goal in the clinic is then to understand the effective dose in patients. So our next step starts are to sweep in nonclinical side and stand from there, also to go into the study of patients that we've been planning and assess those patients and get to an understanding both of what is range and with the effective branch for the study so that we can design dose according to the breadth of this program. 

Jon Stonehouse -- Chief Executive Officer

Yeah. Chris, it's an ongoing chronic tox study right now, and so until we're complete with that target, we'll give you some sense when we'll have a better picture.

Chris Raymond -- Piper Sandler -- Analyst

Thank you.

Operator

The next question comes from Liisa Bayko of Evercore ISI. Please go ahead.

Liisa Bayko -- Evercore ISI -- Analyst

Can you give us a sense of the degree of free drug and sort of gross to net and where you're at for the beginning of 2023?

Charlie Gayer -- Chief Commercial Officer

Sure. Liisa, overall, what we've said is that based on our contract status, we expected at least 80% of patients to be on paid drug, 20% on free. In recent quarters, we've seen that pick up above 20%. And then in Q1, it's just a larger portion that will temporarily -- pretty much all the patients are going through the reauthorization in Q1.

And so a lot of them step back temporarily to free product. So I think overall, that plus the fact that we also have the impact of commercial co-pay assistance is the greatest in Q1 Medicare donut hole payments. You're gonna see the lowest -- the worst gross to net in the first quarter.

Anthony Doyle -- Chief Financial Officer

Yeah. And then it will normalize back up once we get into Q2, 3, 4. When we were in Q4, Liisa, we saw gross demand on reimbursed products at around 15 points.

Liisa Bayko -- Evercore ISI -- Analyst

OK. Thanks. And can you tell us a little bit more -- give us a little more color on the mini expansion that you described, what will come with this?

Charlie Gayer -- Chief Commercial Officer

Yeah. So the basic -- the essence of that was we expanded the number of sales regions. It was not a major sales force expansion, but we made our regions smaller, so added more regional managers so that they can work closely with their teams as well as some of the top KOLs. Then simultaneously, we also added more to our market access team and our patient access specialist team so that we can do more to work with customers and particularly patients to help them get paid therapy. 

Liisa Bayko -- Evercore ISI -- Analyst

OK. Thanks. And then just a follow-up to Chris' question. Are you -- when will you get -- when are you gonna complete this preclinical tox study? 

Jon Stonehouse -- Chief Executive Officer

It will be sometime this year. 

Liisa Bayko -- Evercore ISI -- Analyst

OK. And any sense that you think this might be something specific to the species? And like what species have you been looking at? 

Jon Stonehouse -- Chief Executive Officer

That's a really good question that we don't have an answer to. 

Liisa Bayko -- Evercore ISI -- Analyst

OK. Can you mention the species just for --

Jon Stonehouse -- Chief Executive Officer

Yeah. Not at this time, no. 

Liisa Bayko -- Evercore ISI -- Analyst

OK, OK. And then just final question for me. Are you able to get clinically into what you think is an efficacious dose range? Or as you described going more slowly now in kind of your dose escalation, are you gonna be kind of capped below what you think is the target efficacious dose? 

Jon Stonehouse -- Chief Executive Officer

Our hope is that we get to an effective dose in a safe range. I don't think we can answer that question today, given what we're seeing, but that's the hope.

Helen Thackray -- Chief Research and Development Officer

And I would add, we already know from the data that we presented in January, we're seeing excellent impression of the alternative path we have completed 24 hours already with the dose that we've been evaluating frontiers. So we have more to learn about this range, but we'll share that information. 

Liisa Bayko -- Evercore ISI -- Analyst

OK. Thank you. 

Jon Stonehouse -- Chief Executive Officer

Welcome.

Operator

The next question comes from Jon Wolleben of JMP Securities. Please go ahead.

Jon Wolleben -- JMP Securities -- Analyst

Hey, thanks for taking the question. Just a couple on ORLADEYO. Wondering if you could tell us what the quarter-over-quarter patient growth was in fourth quarter. And then with regards to the $320 million guidance, what's the breakdown between U.S.

and ex-U.S. contribution there? 

Charlie Gayer -- Chief Commercial Officer

Sure, Jon. We haven't specified the growth. What I can say is we are on the same trend, both in terms of new patient acquisition that we've seen over the last many quarters, and also our discontinuation rate has been very stable. So what that means is that every quarter, we're growing nicely, and that's what gives us so much confidence in the $320 million this year and the long-term projection to $1 billion.

And --

Anthony Doyle -- Chief Financial Officer

Yeah, I think in terms of contribution from -- the way I think about it, Jon, is U.S. continues to be the majority of revenue. When we get to a point and we will get to a point, hopefully where we'll split out U.S. and ex-U.S., that will be when ex-U.S.

accounts for around 10% of total revenue. When that will be will be. But at the moment, we're doing really well in both the U.S. and from a global expansion perspective. 

Jon Wolleben -- JMP Securities -- Analyst

Very helpful. Thank you.

Operator

The next question comes from Ken Cacciatore of Cowen & Company. Please go ahead.

Ken Cacciatore -- Cowen and Company -- Analyst

Hey, team. Good morning. Obviously, it's been a fantastic launch of ORLADEYO. You set up a U.S.

commercial infrastructure that would seemingly be attractive to many companies either don't have a U.S. infrastructure would want some further leverage. I'm guessing just looking at the P&L, the product is now profitable, which is a credit to the organization, excluding R&D, and you did it fast. But just -- we often or we rarely, I should say, see such a gap between a profitable product and kind of pipeline replenishment.

Just wondering how you all think about maximizing the value of this dichotomy, which is gonna grow a little bit now, unfortunately, over time here, kind of an organization that's, OK, a little bit in two separate worlds. Can you just talk about that, how you think about maximizing that value and maybe kind of just strategically what you all are thinking? Thanks so much.

Jon Stonehouse -- Chief Executive Officer

Yeah. Thanks, Ken. We agree with you that it's off to a fantastic launch and have a real high degree of confidence that we're getting to the $1 billion in peak sales, and we're on that trajectory. So -- and that it's -- on a stand-alone basis, it's profitable today.

And I even said in my prepared remarks that with the investments that we're making, we're getting closer to profitability because revenue is growing faster than expense basically. So anyway, I think we're always looking -- the goal here is to have a second product that's as big or bigger than ORLADEYO. That may take us longer with our pipeline, and so we're also evaluating BD activities as well. We brought Clayton Fletcher on board recently, who's a very experienced biotech BD person.

And we're probably getting more inbound stuff than we ever have in the history of BioCryst. So we'll continue to evaluate that stuff. You wanna make sure that if you're bringing something in, it's something that can create real value, and so we're constantly looking at that as well. 

Ken Cacciatore -- Cowen and Company -- Analyst

Thank you.

Jon Stonehouse -- Chief Executive Officer

Welcome.

Operator

The next question comes from Justin Kim of Oppenheimer. Please go ahead.

Justin Kim -- Oppenheimer and Company -- Analyst

Hi. Good morning. Thanks for taking the question. Just with the upcoming Quad AI meeting and based on the recent commercial progress, is there anything that needs to be better clarified with the prescriber base in attendance? Just wondering, sort of what your goals are? And any changes in the dynamic of where new scripts are coming from, either from a patient perspective or a clinician?

Charlie Gayer -- Chief Commercial Officer

Hey, Justin. So I think as far as clarify, we're just continuing the messages that we've been delivering about how well ORLADEYO is working in patients, particularly over the long term. You look at our long data, 96-week data, where patients were getting down to 16 out of 17 months attack-free. What we'll see at Quad AI is more data of the same coming out from our clinical trials that confirm that, and so it's really just about getting to all these physicians and showing them how well ORLADEYO work close in clinical trials and then now how well it's working in the real world, and then how well it works regardless of where patients are coming from.

So some of the patients who do absolutely the best on ORLADEYO are those who switch from other prophylaxis products that were already stable on those other products that switched to ORLADEYO, and they continue to do really well with very good in changing control. So that's -- it's sort of a long-term building of that, and there are lots of doctors who already get that. And then there are others who just haven't absorbed that message yet, and we're confident that we're gonna get them as well.

Jon Stonehouse -- Chief Executive Officer

Yeah. I think the other thing, Justin, is that there are docs out there that they're patients-controlled, and that's good enough for them. And so what we've got to be able to do is say, no, a patient could do a whole lot better in terms of burden of therapy if they want to a once-daily oral and to chip away at that. And I think part of Charlie's expansion, where we're having the regional business directors focus on KOLs is to get those potential high prescribers to start to break through even further, get the ones that haven't prescribing the ones that have to prescribe more.

Justin Kim -- Oppenheimer and Company -- Analyst

I guess I'm just sort of curious, in terms of your views on the long-term growth trajectory, is that mix of where the script is coming from expected to change, whether between the 500 and non-500 space? I mean just trying to understand if that split of 50-50 is expected to continue and then for how long? 

Charlie Gayer -- Chief Commercial Officer

I think it's a good question. First of all, I'm really happy with that balance because what it shows is that we're reaching all parts of the market, and we're growing in both segments. So we're constantly expanding the number of top 500 doctors who are new ORLADEYO prescribers, and then we're seeing them once they go deeper into their list. And then that next 1,000 or so doctors, we're expanding into them as well.

So there's -- what it tells me is there is a lot of opportunity left in front of us, both among what HCPs can do and then the number of patients that still haven't experienced the benefit of ORLADEYO. And our goal long term is to give every patient who needs to be on prophylaxis a chance to try ORLADEYO because most of them are gonna do really well. 

Jon Stonehouse -- Chief Executive Officer

Yeah. I think there's two really interesting pieces of evidence that we're going in that direction, too. One is quarter to quarter, we're expanding the prescriber base, and the second is the market research quarter after quarter after quarter says that docs are gonna prescribe more in 12 months than they're currently prescribing. And that's a combination of people who have not yet prescribed that will in the future or those that are prescribing that will prescribe more.

So those we think are two really encouraging pieces of data that give us a lot of confidence it's gonna keep growing. 

Justin Kim -- Oppenheimer and Company -- Analyst

Thanks so much.

Jon Stonehouse -- Chief Executive Officer

Welcome.

Operator

The next question comes from Brian Abrahams of RBC Capital Markets. Please go ahead.

Brian Abrahams -- RBC Capital Markets -- Analyst

Hi. Good morning. Thanks for taking my questions. You guys have talked about a recent slower conversion from free drug to paid commercial drug in fourth quarter and of late, and I just wanna better understand this trend.

Do you think this is reflecting just expanding to new physicians who may be less used to prescribing ORLADEYO? And are there ways to help educate those physicians about how to process the necessary paperwork? Or is there anything different about these patients, either they have milder disease, or more on prior prophylaxis, or have different types of insurance plans that may be contributing to this greater lag time? And then just real quick on 10013. Were the preclinical findings you observed shared with relevant regulators? And is there any need to, I guess, pause dosing? Or should we just expect you'll be looking at shorter durations and/or lower dose levels as the clinical studies proceed? Thanks.

Charlie Gayer -- Chief Commercial Officer

I'll take the first question, Brian. Yeah. So it's really much more of the first thing you said. So as we're expanding to less experienced prescribers within the HAE space, it works to get any drug, whether it's ORLADEYO or any other HAE therapy approved by insurers.

It's not a contracting issue. It's really about providing all the information, the lab test, the clinical history, the complete information that payers want to see before approving any treatment for HAE. And so that's a big part of the team expansion that we've described. So we have more people out there to help with this process to get patients to paid therapy, and it's really about having a very complete prior authorization and reauthorization to make sure that we help them give all the information that the payers need.

So I'm actually -- with what I'm seeing, I'm confident that we are gonna make great improvement in this ratio of pay to free product. It's not all gonna be in Q1. It's gonna be a year-long process, but I think we are very much on the right track. 

Jon Stonehouse -- Chief Executive Officer

Helen, do you wanna take the 10013? 

Helen Thackray -- Chief Research and Development Officer

Yeah. So a question on 10013, so this is the nonclinical information we're reporting today. This is an ongoing study, and so we still have more to learn here. We always are in close touch with regulators over, what's going in and what data comes in programs that's not clinical and clinical.

We have deferred the higher dose levels in our healthy volunteer study. Absolutely, there's more about this information, but we do still plan to go forward in patients that take the drug therapeutic range in patients to understand there. What we're saying is that as the nonclinical data informs your understanding of the range of exposures, we expect it will have some delay in how high we go to the faster dose or how fast we go to the higher doses in patients in the study.

Charlie Gayer -- Chief Commercial Officer

And Brian, if I could just come back, I realize that probably I didn't answer part of your question, which is just on patient mix. It doesn't have anything to do with the patient mix. It's all about the other mix that I described, just giving the doctors -- or sorry, giving the plans or the information that they need. And remember, half of our patients since launch have been patients switching from all the prophy products.

So it's really -- it's not about the patient mix.

Brian Abrahams -- RBC Capital Markets -- Analyst

That's really helpful. Thanks, Charlie. Thanks, Helen. Appreciate it.

Operator

The next question comes from Maury Raycroft of Jefferies. Please go ahead.

Maury Raycroft -- Jefferies -- Analyst

Hi. Good morning, and thanks for taking my questions. I was wondering for Quad AI later this week, if you can provide some preview around observed similarities or differences in treating pediatric HAE patients and remind what the sNDA timeline could look like. And how does the pediatric opportunity fit into your $1 billion peak sales estimate?

Charlie Gayer -- Chief Commercial Officer

Sure. So where we are with our pediatric clinical trial, it's open, it's been rolling. And so it's -- it will take a little time to get that fully enrolled until we get to the sNDA. But what we're seeing and one thing that we'll present this week at Quad AI is just the overall burden of treatment and of HAE identified by both caregivers, parents, and patients.

And one thing we hear over and over again is when a kid has symptomatically shaping up, the -- sometimes the treatment is injectable, can be worse than -- almost worse than the attack themselves. It could be really dramatic for kids to have regular injections or infusions, and so there's just real demand for an oral therapy to help these kids. And so we have -- long term, we think that this is gonna be -- it's not so much about the number of patients treated. It's about the fact that we're gonna be able to make the lives better for a lot of these kids.

And then, of course, it's a genetic disease, so we see typically families will often use the same types of product, and so it gives us an opportunity to kind of tell the ORLADEYO story to a complete family, which we really look forward to.

Jon Stonehouse -- Chief Executive Officer

I think the other thing, Maury, is the formulation that we have for this is -- we used to call it mini tabs. What do we call it, granules now? But it's like sprinkles as you put on a cake almost at that size. And so asking a little kid to take a capsule is a difficult thing, too. So we've come up with a formulation that you could put on apple sauce, on yogurt, and just make it way less dramatic, along the lines of what Charlie was describing.

And that will be huge. And then this is a patient for life, right? And so it's not a huge market, but we think it's an important one, and we think these are customers that we could have for a very long time. 

Maury Raycroft -- Jefferies -- Analyst

Got it. That's helpful and makes sense. And maybe one other quick question. Just for the 10013 delays, is that factored into the $375 million opex assumptions for next year? Can you talk more about opex assumptions in general for next year -- for this year?

Anthony Doyle -- Chief Financial Officer

Yeah. So it's -- the way to think about opex for the year, so flat year over year, but what we've said is that commercial expenditure is going to increase based on the additions that Charlie has talked about predominantly here in the U.S. as well as expansion from a global perspective, given that we're now in 15 countries and we'll be going to more. For R&D, the delay is factored in depending on what we see on an ongoing basis.

That may change when we get more information, and we'll update that later in the year. But yes, it is currently factored in. And what we said about R&D is it's going to decrease year over year anyway. When we were talking about this about a quarter ago, we said it was gonna be flat, now we're saying it's gonna be down, but offset by the commercial investment that we've seen.

And then most importantly, with revenues increasing and then seeing that flattening of the opex line and then the convergence of those two lines, the net cash utilization and what that means as we move toward profitability, I think, has a lot of value for the company. 

Maury Raycroft -- Jefferies -- Analyst

Got it. Thanks for taking my question.

Operator

The next question comes from Gena Wang of Barclays. Please go ahead.

Gena Wang -- Barclays -- Analyst

Thanks for taking my question. The first one is regarding 10013. So just want to confirm, is it fair to say that we should not expect the FDA clinical hold regarding this program? And then my second question is regarding the ORLADEYO. In early January, you mentioned that the retention rate is about 60%.

Can you clarify if that is one year or three months retention rate? And also, do you expect a similar retention rate maintaining in 2023? 

Helen Thackray -- Chief Research and Development Officer

So the first question on 10013, we're not on clinical holes with this program. There's -- it's a little difficult to say what will happen in the future, so that's where we are today.

Charlie Gayer -- Chief Commercial Officer

And as far as the patient retention, Gena, yeah, 60% of that one year, and we would expect -- what we're seeing in the overall retention rate is it's really stabilizing out. And so that's part of our confidence in no less than $320 million this year, and so we'd expect the same retention trend overall in 2023. 

Gena Wang -- Barclays -- Analyst

Thank you.

Operator

Our last question comes from Rohit Bhasin of Needham & Co. Please go ahead.

Rohit Bhasin -- Needham and Company -- Analyst

This is Rohit on for Serge. Thanks for taking our questions. Just in terms of peak sale estimates, do you still expect about 20% to 25% to come from ex-U.S. territories? And can you talk about your expectations for the long-term competitive landscape for ORLADEYO? Thanks.

Charlie Gayer -- Chief Commercial Officer

Sure, Rohit, absolutely. So when we talk about the $1 billion, we still see about 20% of that coming from Europe and the rest of the world, and all the trends in those in the 15 countries where we've launched so far give us confidence that we will get to that 20% on that at peak.

Jon Stonehouse -- Chief Executive Officer

And then with regard to the competitors, it's a pretty crowded space. But with regard to oral specifically, it's been challenging for some to advance their programs. And so what that means for us is we have more time to get people to try our drug and see if it works for them. And what we've learned in the marketplace is to get people to switch, there's got to be some meaningful benefit that they're not seen with the drug that they're on.

And it can't be efficacy because if you're on our drug, you're controlled. If you're not controlled, you're not staying on our drug. So -- and so that goes for injectables as well. And I think a tailwind that we're curious, Charlie has pointed this multiple times, but we'll be curious to see is as new products come to market.

If a physician is saying, hey, maybe I'll switch from one injectable to another. Why wouldn't they try an oral first? And then if it didn't work for that patient, switch to the new injectable. So it could be a tailwind. 

Rohit Bhasin -- Needham and Company -- Analyst

Thank you.

Jon Stonehouse -- Chief Executive Officer

You're welcome.

Operator

[Operator signoff]

Duration: 0 minutes

Call participants:

John Bluth -- Senior Vice President, Investor Relations and Corporate Communications

Jon Stonehouse -- Chief Executive Officer

Charlie Gayer -- Chief Commercial Officer

Helen Thackray -- Chief Research and Development Officer

Anthony Doyle -- Chief Financial Officer

Jess Fye -- JPMorgan Chase and Company -- Analyst

Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst

Chris Raymond -- Piper Sandler -- Analyst

Liisa Bayko -- Evercore ISI -- Analyst

Jon Wolleben -- JMP Securities -- Analyst

Ken Cacciatore -- Cowen and Company -- Analyst

Justin Kim -- Oppenheimer and Company -- Analyst

Brian Abrahams -- RBC Capital Markets -- Analyst

Maury Raycroft -- Jefferies -- Analyst

Gena Wang -- Barclays -- Analyst

Rohit Bhasin -- Needham and Company -- Analyst

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