BioCryst Pharmaceuticals Inc

NASDAQ:BCRX

Earnings Call Analysis

Strong Revenue Growth and Positive Outlook for ORLADEYO

BioCryst had an impressive Q2 with ORLADEYO generating $108.3 million, a 34% increase year-over-year. This performance led to raising 2024 revenue guidance to $420-$435 million. Paid patient rates improved from 71.5% to 74.4%, and U.S. sales contributed $95.9 million of total revenue. Operational investments are paying off, driving strong patient retention and compliance. The company also aims for long-term revenue of $1 billion. The global expansion is robust, with ex-U.S. sales up 51%. BioCryst remains focused on pipeline progress with new therapies for rare diseases, maintaining a strong path towards profitability.

Strong Q2 Performance

In the second quarter of 2024, BioCryst Pharmaceutical's flagship product ORLADEYO achieved remarkable global revenue of $108.3 million, a significant 34% year-over-year increase. This surge in revenue demonstrates the growing demand for ORLADEYO, as it retains a usability rate that's notably appealing to patients. The company attributed this growth to a combination of higher patient compliance and effective operational improvements.

Guidance and Revenue Projections

Based on the stellar performance in the second quarter, the management has confidently raised its full-year 2024 revenue guidance for ORLADEYO to between $420 million and $435 million. This marks an increase of $30 to $35 million compared to prior guidance and represents approximately a $100 million increase over last year’s total revenue. This optimistic outlook signals strong market performance as they approach their long-term goal of reaching $1 billion in peak global revenue.

Operational Efficiency and Cash Management

Operating expenses were reduced to $87.4 million for the quarter, showcasing effective cost management efforts. The company's guidance for full-year operating expenses remains unchanged at between $365 million and $375 million. Moreover, BioCryst reported a net cash utilization of just $213,000 in Q2, below their guided expectation of $10 million to $12 million per quarter, reflecting improved cash flow management. The company expects to continue operating at single-digit million dollar utilization for the remainder of the year.

Market Positioning and Patient Engagement

BioCryst reported that approximately 82% of commercially insured patients using ORLADEYO are now on paid therapy, a significant increase from 72% at the end of 2022. The company sees a clear path towards achieving their long-term objective of 85% paid treatment in the U.S. market. Notably, they have identified that nearly half of the patients switching to ORLADEYO are previously on injectable therapies. With the current total market of over 11,000 HAE patients in the U.S., they are nearing a market share of approximately 20%.

Growing Physician Confidence and Patient Retention

Physician confidence in ORLADEYO continues to rise, with recent surveys indicating that over 90% of treating physicians consider prescribing the drug. This confidence correlates with strong patient outcomes; 80% of ORLADEYO users reported fewer attacks compared to prior treatments. The retention rate for patients who started on ORLADEYO is competitive, with notable figures showing 61% of prior prophylaxis patients and 67% of treatment-naive patients remaining on therapy after a year.

Global Expansion and Future Opportunities

The global sales of ORLADEYO also showed impressive growth, with international sales rising by 51% year-over-year, highlighting the company's effective expansion strategies. Sales outside the U.S. accounted for $12.4 million of the revenue in Q2, aided by access in over 20 countries. Looking ahead, the company plans to file for approval of ORLADEYO in younger children by next year, marking a significant milestone and a potential expansion of their patient base.

Pipeline Developments

Beyond ORLADEYO, BioCryst is also making advancements in its pipeline, particularly with the KLK-5 inhibitor for Netherton syndrome, expected to begin human trials later this year. Their commitment to advancing rare disease therapies complements a strategic focus on building long-term revenue streams beyond the flagship product.

Conclusion

Overall, BioCryst is demonstrating solid growth and operational efficiency, as reflected in their latest earnings call. With a promising revenue outlook and increasing confidence among both patients and physicians, the company appears well-positioned for continued success in both domestic and international markets. Investors may find the combination of solid cash management, a strong product pipeline, and robust market demand compelling as the company strives towards its long-term goals.

Earnings Call Transcript 2024-Q2

[Operator]

Good day, and welcome to the BioCryst Second Quarter 2024 Earnings 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, executive]

Thanks, Dave. Good morning, and welcome to BioCryst's Second Quarter 2024 Corporate Update and Financial Results Conference Call. Today's press release and accompanying slides, which we'll be referring to 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. 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.

In addition, today's conference call includes non-GAAP pro forma financial measures. For a reconciliation of these non-GAAP measures against the most directly comparable GAAP financial measure, please refer to the earnings press release posted in the Press Releases section of our Investor Relations website at www.biocryst.com. I'd now like to turn the call over to Jon Stonehouse.

[Jon Stonehouse, executive]

Thanks, John. Our second quarter performance with ORLADEYO is nothing short of amazing. Especially when you recall the great start we had in the first quarter. This performance is due to the confidence we are seeing from our customers since late last year, and it continues to build. Physicians who treat HAE and many of their patients are experiencing firsthand how well ORLADEYO works and that they can achieve this control with an oral once-daily therapy, efficacy and convenience.

Many patients are experiencing efficacy similar to what they had on injectable therapy. As a result, halfway through the fourth year since approval, we are experiencing demand as strong as the start of the launch. Amazing. This confidence has also led us to increase our guidance for the year to between $420 million and $435 million. Charlie will provide more details on the quarter and share why the evidence is increasingly clear. We are on a path to $1 billion in peak. I'd also like to give you an update on our pipeline. Remember, our goal with this investment is to bring to market our next meaningful therapy to patients living with rare diseases like we did with ORLADEYO.

We continue to make great progress overall advancing our programs. First, we remain on track to file for approval in younger children down to 2 years of age with the oral granule formulation of ORLADEYO next year. This is a very important patient population whose parents have been waiting for this therapy. Think about it. If your child is having HAE attacks, the only current treatment is injecting them, any parent knows how traumatic that is. So to bring a therapy, they can sprinkle in a glass of water or on soft food is a game changer for these families. We are wrapping up the trial and preparation is in full gear for this filing and launch.

Next, I'd like to update you on BCX10013, our oral Factor D inhibitor. We have shared data from the PNH dose-ranging clinical trial with potential partners. There were no safety concerns. The drug has been safe and well tolerated at all doses studied. However, while we are seeing some activity in PNH patients, the effect seen was less than other therapies on the market.

As a reminder, early this year, we announced that we had planned to stop spending on the program and reduce staff accordingly while seeking a potential partner. Potential partners have declined to make the additional investment required to evaluate higher doses. Therefore, we will now discontinue development consistent with the plan we described in January.

Regarding the rest of the pipeline, we have 2 exciting new molecules moving towards the clinic. We remain on track to start dosing healthy volunteers this year with our KLK-5 inhibitor BCX17725 for patients living with Netherton syndrome. We are also on track to begin dose-ranging patients in our DME clinical trial next year with avoralstat. This will likely give us data in patients in both programs by next year to inform us on activity and dose. So exciting progress in both programs. Finally, our complement programs with our bifunctional fusion protein and oral C5 inhibitor are also progressing towards selecting lead candidates.

Let me wrap up with 2 more important points. First, we are committed to accelerating our path to profitability to become independent of the capital markets for funding. Anthony will share more details, but we are well on our way to delivering on that commitment. And second, our impressive performance this quarter and for the first half of this year is a direct reflection of the commitment our employees have to our patients. This was an amazing quarter of performance on many fronts, and I want to thank every BioCryst employee for getting us here and for the momentum they have created to continue this throughout the remainder of the year. Now I'd like to turn it over to Charlie to review the ORLADEYO quarterly performance.

[Charles Gayer, executive]

Thanks, Jon. It was an absolutely great quarter with over $108 million in global revenue against our expectation of $97 million. Demand rate remained strong and was the key driver of our 34% year-over-year revenue growth. New patient prescriptions for the past 3 quarters continued to equal the high demand we experienced in the very first 3 quarters of the launch 3 years ago but operational improvements made the immediate difference that drove our performance in the quarter.

The investments in our team that we have described previously are paying off significantly. The percentage of -- on paid therapy, for example, is up nearly 3% since the end of 2023 from 71.5% to 74.4%. This is ahead of our expectations. Of note, we are up to a paid patient rate of 82% among commercially insured patients. Recall that about 60% of our patients are commercial, and the paid rate in this segment is up from 79% at the end of 2023 and 72% at the end of 2022. This progress makes our long-term expectation to reach 85% paid even more clear. Other aspects such as increased patient compliance and retention against our Q2 expectations added to the great result, and we see these improvements being sustainable.

With that base of improving operations, let's move to the long-term demand and overall market opportunity. Patients have long told us that they want a convenient oral route of administration to prevent attacks, but they won't compromise on efficacy, and nor will their physicians. Our long-term data and real-world evidence are convincing patients and their physicians that both are possible with ORLADEYO, efficacy and convenience. The cornerstones to this motivating message 91% reduction in attacks versus baseline in our pivotal trial and the growing and consistent body of real-world evidence that reflects the favorable experiences of individual patients and physicians, all with 1 capsule once a day. Physicians are increasingly confident that ORLADEYO will be effective as well as convenient for their patients. And physician confidence translates to patient confidence, particularly for the many patients who would prefer oral prophylaxis therapy regardless of their treatment history.

Slide 8 of today's presentation shows that 52% of all patients starting ORLADEYO to date, switched after having experience with other HAE prophylaxis therapies, 32% with a history of on-demand treatment only and 17% were treatment naive. Again, regardless of their prior treatment experience, most patients do well.

As you can see on Slide 10, 61% of prior prophy and 67% of prophy naive patients who start on ORLADEYO and reach paid status stay on therapy for at least a year. What's notable is that patient retention is similar, whether patients are starting ORLADEYO or injectable prophylaxis as you can see from a preliminary analysis of claims data on Slide 11. This is not surprising, at least to us, based on our internal data and what we hear from patients, but this point is worth repeating. There is no statistical difference in 1-year retention for patients starting ORLADEYO, lanadelumab or C1 inhibitor prophylaxis. I will point out, however, that the 1-year retention on ORLADEYO of 61% is numerically higher than the other 2.

So why are patients staying on ORLADEYO at such high rates, rates that are comparable to other prophy therapies. Patients have told us individually and in large market research studies that they would prefer to control their attacks with a daily pill. This includes half the patients currently on injectable prophy, as you can see from a recent survey of 120 patients shown on Slide 12. They share their [indiscernible] to switch in that same market research study, no needles, no preparation, freedom to travel feeling normal and forgetting they have HAE are all part of their dream. ORLADEYO is delivering on that dream.

In large -- in results from large surveys of patients taking ORLADEYO, you can see -- that you can see on Slide 14, approximately 80% said they are having fewer attacks than they did before starting on ORLADEYO, and about 75% told us they are having less severe attacks. Overall, about 9 in 10 patients told us their attack control was at least as good as it was previously. And yes, those patients who switched from injectable prophylaxis told us the same thing. This is what efficacy and convenience looks like. So what does this lead to?

Well, recent market research with large samples of allergist/immunologist shown on Slide 15 indicates that over 9 in 10 HAE treaters now consider prescribing ORLADEYO for their patients, and over 50% of current prescribers are extremely likely to prescribe again compared to under 30% a year ago. That is a big shift over a year. Why have they shifted? Because they have seen the evidence. Not only have we shown it to them, but they have also heard the evidence directly from their patients.

This increasing enthusiasm for physicians matches well with the considerable opportunity that remains for ORLADEYO. For example, the market research on Slide 12 shows that 3 out of 4 patients currently on injectable prophy are willing to switch.

We also have updated administrative claims-based studies to size the market that you can see on Slide 9. Since we first did these studies prior to the ORLADEYO launch, the number of treated HAE patients in the U.S. has grown to 8,500, and the total number of patients -- of HAE patients has increased to over 11,000.

As I described earlier, patients from all segments are benefiting from ORLADEYO with comparable success in treatment outcomes, patient retention and rate of paid therapy. Even with the strong first 3 years of the launch and the 2,500 prescriptions through the end of 2023, fewer than 1 in 4 U.S. HAE patients has tried ORLADEYO. With a high patient desire for oral therapy and the growing physician intent to prescribe, there is way more opportunity in front of us than behind us.

Finally, it is also increasingly clear that our global expansion is working. Ex U.S. sales in the second quarter were $12.4 million, up 51% year-over-year. We recently exceeded 500 patients in Europe, and we are already selling ORLADEYO in over 20 countries globally with many more actively preparing for market authorization, access and launch.

To summarize, the operational improvements we saw in Q2 on top of what we saw in Q1, mean that the increasing paid rates in high patient compliance are sustainable. And we are on track toward our long-term goal of 85% paid treatment in the U.S. In addition, patient and prescriber confidence are growing stronger because both groups are experiencing not just the convenience, but also the efficacy of ORLADEYO.

We have been describing $1 billion in peak global revenue for ORLADEYO for a few years now. The path to that sustainable peak is increasingly clear. Now I'll hand the call over to Anthony to describe our financial performance.

[Anthony Doyle, executive]

Thanks, Charlie. It's very encouraging to see yet another really strong quarter for ORLADEYO. It's great work with our team. You can find our detailed second quarter financials in today's earnings press release, and I'd like to call your attention to a few items. Total revenue for the quarter was $109.3 million. And as Charlie said, $108.3 million of that came from ORLADEYO. That's a 34% increase in ORLADEYO revenue over the same quarter last year and ORLADEYO revenues in the past 12 months are over $373 million. Of the $108.3 million of Global ORLADEYO revenue, $95.9 million came from U.S. sales with the remaining $12.4 million or 11.4% coming from ex U.S. sales.

Operating expenses, not including noncash stock compensation for the quarter were $87.4 million, a decrease of $6.2 million from Q1 of this year and a decrease of $3 million from Q2 of 2023. Full year 2024 guidance for OpEx remains unchanged at between $365 million and $375 million. We achieved an operating profit for the quarter of $21.9 million, excluding noncash stock comp and an operating profit of $8.8 million, even when including noncash stock comp, which was $13.2 million for the quarter. Cash at the end of the quarter was at $338.1 million, and net cash utilization for the quarter was just [ $213,000 ]. We had guided to net cash utilization of between $10 million to $12 million per quarter for the remainder of the year. The main driver for the improvement in cash flow for Q2 was the increase in revenue versus forecast of over $11 million.

For the remaining 2 quarters of 2024, I expect net cash utilization to average out at single-digit millions of dollars per quarter. We're even more confident in our guidance of having quarterly positive cash flow late next year and more strong quarters like we saw in Q2 may help us to accelerate that.

To be clear, from both an operational and a financial perspective, Q2 was a stellar quarter. Let's also be clear, that this is not a one-off or an anomaly. The performance of the commercial team, both in the U.S. and ex U.S. since the launch of ORLADEYO has been nothing short of terrific. And yes, Q2 overachieved even our initial expectations. If ask, was this a surprise? I would answer, no. I stopped being surprised given what this team has achieved since launch and given the immense success that we have seen patients have while on ORLADEYO to achieve both efficacy and convenience with this best-in-class drug.

This continued strength is what gives us the confidence to increase our 2024 revenue guidance for ORLADEYO so significantly to between $420 million and $435 million, a $30 million to $35 million increase in the range and an approximate $100 million increase over last year's total.

As another positive, the entirety of that additional $30 million to $35 million is at the lower royalty rate of 7.5% which would bring the blended royalty rate down by 30 to 50 basis points versus our prior guidance. With OpEx guidance unchanged at flat to last year, we're even more confident about our past profitability with an operating profit for full year this year, EPS and cash flow positivity on a quarterly basis next year and full year EPS positive and cash flow positive in 2026.

Operator, we'll now open it up for Q&A.

[Operator]

[Operator Instructions] Our first question comes from Tazeen Ahmad.

Tazeen Ahmad with Bank of America. We're going to transition to Jessica Fye with JPMorgan.

[Elias Lenard, analyst]

This is Nick on for Jessica. Congrats on the quarter. So based on these results, including the updated guidance for ORLADEYO and maintained expectations around operating expenses, could you discuss your level of feeling around if you could reach GAAP operating profits in 2024 and not just full year operating profit, excluding noncash stock compensation?

[Anthony Doyle, executive]

Yes. Q2 as it relates to both revenue and our control on operating expenses, like we said, were terrific. And so what we have guided to previously was getting there not including noncash stock compensation, we're still guiding to that. Is there a chance that we would get there, even including the noncash stock compensation. Absolutely. It just depends on for the remainder of the year, revenue and then the offset between that and OpEx, but what I would guide to is our increased confidence of getting there excluding noncash stock comp.

[Elias Lenard, analyst]

Okay. And then within that raised guidance for ORLADEYO, can you just discuss in a bit more detail your underlying assumptions around new patient starts, the percent of patients on paid drug and maybe compliance retention for the remainder of the year. And how that changes -- could change versus 1Q and 2Q?

[Charles Gayer, executive]

Sure. Yes. Nick, we've -- as you know, we've reported very consistent new patient starts. And then the last 3 quarters have been even stronger as strong as the first 3 quarters of the launch. So we would expect the consistent demand to be based on all the metrics that I described today. As far as paid rate, like I said, we're ahead of our expectations. We are not expecting major increases for the rest of the year.

The goal is to at least hold back consistent with the 74.4% that we were at the end of Q2 and compliance is just really strong. So compliance at this point, if you measure it by the number of treatment days available to the -- your overall patient population and then the number of drug days basically delivered. We're in the mid-90s at this point, and we would expect that to continue.

[Operator]

And our next question comes from Tazeen Ahmad with Bank of America.

[Tazeen Ahmad, analyst]

Can I ask a question about the pipeline. Your focus now another 10 disease. Maybe can you talk about the data that you've collected internally that gives you confidence in pursuing this particular molecule for this indication and maybe the cadence of data to expect over the next year or so?

[Helen Thackray, executive]

Sure. So let me take that last piece first. The cadence is that we -- for 17725 we're proceeding into first-in-human this year. And so that's an important milestone to keep in mind for this program. In terms of the data that we have to support that, we have all of the required data to be able to proceed to first-in-human, generally that includes safety from a nonclinical toxicology perspective as well as data to support the importance of the mechanism for treating the disease and the potential to improve clinical symptoms in patients.

So we have nonclinical data for both safety and efficacy that's supported the proceeding to humans. We also have data around the likely exposure range, and we will be going to first-in-human this year.

[Jon Stonehouse, executive]

Yes. And Helen and I were in Birmingham this week, and we got to see the animal model work that the team is working on. It's an inflammation model, and it was really impressive what we saw, the control animals have an inflammation and then the inflammation going down with each higher dose. So the key is that you not only have good drug levels, but the drug levels get to the target, which is the skin and so far, so good. So we're hoping we'll see that in humans as well.

[Operator]

Next question comes from Brian Abrahams with RBC Capital Markets.

[Brian Abrahams, analyst]

Congrats on the quarter. I'm wondering if you could maybe elaborate a little bit more on why we saw such a big uptick in the paid drug just on a quarter-over-quarter basis and maybe some of the seasonal trends underlying that versus kind of operational trends? And then can you talk a little bit more about the inputs that went into your resizing of the HAE market and I guess, just in -- with the additional 1,000 patients and just kind of wondering if you can talk about the characteristics anything you've learned about those additional patients who are out there, how accessible they are, what you might need to do to engage them?

[Charles Gayer, executive]

Brian, first off, on the uptick in the paid as I mentioned in my comments and we've talked about this before, we've invested a lot in the team to really make sure that we are helping patients and health care providers do everything possible to not only put in a kind of a complete start form upfront, all the information that payers want, but then to go through the appeals process when that's necessary.

And since we made that investment last year, I think the team is really hitting stride and that's what's making the difference. It's not a seasonal factor in Q2. I mean Q1 is really the seasonal time with the reauthorization. But now it's just really about every single patient and the -- just the operational improvements that we've made. So I'm really, really pleased with their progress. As far as the resizing of the market, we've done this kind of work with claims data regularly. And you'll recall that prior to launch, we talked about 7,500 diagnosed and treated patients.

We knew that there was a larger population of untreated patients but we were conservative in those initial numbers that we put out. What we're seeing now with ORLADEYO attracting patients from all segments, from prophy switches, from on-demand only and then also treatment-naive patients. We're attracting all three. And so we redid the numbers. We've seen that the market has grown. We think a good portion of that growth is due to our promotion with ORLADEYO. And so we thought it was time to update the overall...

[Operator]

And the next question comes from Chris Raymond with Piper Sandler.

[Christopher Raymond, analyst]

Congrats on the progress. Great to see. Just on, maybe one question on ORLADEYO, one on the pipeline. So it was kind of struck by your patient activation side with the market research showing that essentially 3 and 4 patients are willing to switch. Can you maybe give a little bit more color on as you sort of distill those patients down, how do you activate those patients that would seem to be a dynamic, that would indicate -- you certainly understand why your guidance has been raised here. But that there's maybe a little bit more opportunity if you can really convert all those patients. So maybe how many of those do you think are really candidates for activation.

And then maybe just a pipeline question. With respect to the Netherton syndrome program, just maybe talk about why you think a KLK-5 inhibitor would be effective in this population. And just looking at some of the other programs that are in this disease, talk about maybe how you look at the differentiation?

[Charles Gayer, executive]

I'll start with the question about the patient activation. Yes, we're thrilled to see that so many patients are willing to switch and so many patients who are on injectable prophylaxis and that that's continued and actually grown throughout the launch. We have a number of ways that we try to activate them. We have extensive digital marketing, other kind of direct marketing programs to patients -- but I'll say the #1 way to activate them is to make them aware that ORLADEYO is out there and then to make sure that their health care providers are confident in the product.

And what you can see from the data I've shown you today is physicians are increasingly confident. And I think when physicians have that conversation with their patient about all of their treatment options, you combine that with a patient -- the strong patient desire for oral therapy and the willingness to switch, that is what is going to activate more patients to switch. That's going to be the strongest driver.

[Jon Stonehouse, executive]

Maybe I'll start and then pass it to you. So it's a great question because we're really excited to bring something forward that actually treats the underlying disease rather than the inflammation and the system. The inflammation due to the disease, but I'll let Helen talk a bit more about it.

[Helen Thackray, executive]

Yes. Thanks, John. So KLK-5 is dysregulated in Netherton syndrome. That's the cause of the disease. So KLK-5 inhibitor is a way to place the function that's missing and improve the cause of the disease. It's -- so we believe we have a differentiated product for this for 2 different reasons. One, we've achieved very, very high potency with our drug, and that means that we could potentially deliver a subcutaneous dose and also deliver it on a less frequent basis than is typical for this type of therapy.

And so two, in terms of the mechanism -- it's important to go back to that KLK-5 dysregulation as the cause of the disease. This -- approaching this target means that you don't just affect the cause of the disease in the skin, you're also affecting the downstream inflammation, whereas some others programs that are in the pipeline for this disease are affecting just the downstream inflammation. So we expect to see healing of the skin and improvement of the disease from that perspective as well as preventing then the downstream inflammation that causes other effects in the disease.

[Jon Stonehouse, executive]

And one of the things you see in rare diseases like this, where there's nothing to treat it is they're way more patients than you originally estimated, and that's really exciting as well.

[Operator]

The next question comes from Gena Wang with Barclays.

[Huidong Wang, analyst]

I also want to add my congrats on the strong quarter. So with revised the guidance just wondering, where do you see the main increase? Would that be mainly from on-demand patient, untreated patients or continue to be from the switchover patient? And then for the pipeline assets, just wondering will you, at some point, sharing the preclinical data?

[Jon Stonehouse, executive]

On which program Gena?

[Huidong Wang, analyst]

The lead asset, the pipeline asset, the 17725?

[Charles Gayer, executive]

Gena, I think what I showed today, we're thrilled that we are getting over 50% of patients from prophylaxis switches. And then we're also getting the on-demand patients and even treatment naive. We expect that to continue.

And the market research that I showed on Slide 12 is specific to patients on injectable prophylaxis and you can see from that, that 50% of the patients have -- of those patients have a preference specifically for oral prophylaxis therapy, and 3 out of 4 -- 3 out of 4 of those patients are willing to switch. And so what I would expect is the same dynamics to continue. About half the patients coming from prophy and then the other half coming from on-demand and treatment naive.

[Anthony Doyle, executive]

While it's great to see that growth this year and growth next year is going to come from that growth in patient demand, the increase in the guidance for this year, a lot of that's driven by the operational activity that Charlie explained. So it's great to see both things happening simultaneously.

[Jon Stonehouse, executive]

Helen, do you want to take the...

[Helen Thackray, executive]

Pipeline. Yes. So in terms of sharing preclinical data, we would, of course, publish data in the future as we have excellent results for our pipeline programs.

In terms of the Netherton syndrome program. Jon mentioned earlier, the data that we have in an animal model showing changes in the skin. We also have a disease -- animal model information showing the extreme potency with this molecule. So we would expect to share data supporting both potency and effect. But for the purposes of today, I think it's important to know that we have sufficient information to be ready to proceed to first-in-human, and we're very excited about this program's potential.

[Jon Stonehouse, executive]

And we're going to have human data by the end of next year. So you're going to start to get a sense of activity and dose by the end of next year, both in this program and the DME of oral step program, which is super exciting.

[Operator]

[Operator Instructions] Our next question comes from Maury Raycroft with Jefferies.

[Maurice Raycroft, analyst]

I'll add my congrats on the quarter. Just a follow-up on the paid patients, improvement this quarter. You said you could potentially get to 85% paid patients over the next few years, but it sounds like you're doing better than expected on this front. At this point, are you able to provide more clarity into when you could achieve the 85% patients on paid track.

[Charles Gayer, executive]

Maury, I think the real key with the 85% is -- that's part of our growth to the $800 million in the U.S. as we achieve $1 billion in peak sales. We previously mapped out a path to that by 2029. We'll try to get there as quickly as we can. But if we get there by 2029, we will achieve that $1 billion. And based on what we've talked about today, it's increasingly clear that we're going to get there. What I'm particularly excited about in -- I noted this in my comments, is the fact that we're at 82% paid already for the commercial segment, which is our biggest segment. And that just shows that we're going to get there. It's just a matter of time.

[Jon Stonehouse, executive]

And Charlie, is it fair to say that next year could be a really interesting year with Medicare patients in particular. And we don't want to project what we think will happen, but there's a possibility that we could make real progress there as well.

[Charles Gayer, executive]

That's right. There's an opportunity to hopefully get a lot of the Medicare patients have not been able to afford their copayments, and that's led them to be on free product with the full introduction of the IRA next year and the max out-of-pocket for patients going to $2,000. That could be an opportunity that creates more affordability and thus, more paid patients.

[Maurice Raycroft, analyst]

Got it. That's helpful. And just to clarify, for the 74.4% for this quarter, you expect that to be consistent for the rest of this year? Or could that potentially improve some as well?

[Charles Gayer, executive]

We will always try to improve it. The time where we can make the biggest progress is during the big reauthorization season in Q1. And we did a great job in Q1 and then some of that great job bled into the early part of Q2. The rest of the year will be driven more by new patient prescriptions coming in, the opportunity to convert long-term free product over to paid will be less than it was in the first part of the year, kind of the seasonal cycle that we should expect going forward.

[Operator]

The next question comes from Stacy Ku with TD Cowen.

[Stacy Ku, analyst]

Congratulations on the progress. So we have a few follow-ups. First, I appreciate your detailed market research, our KOLs and survey also tell us that additional deductible entrants are very unlikely to impact oral prophylactic options in HAE. So curious if Charlie or Jinky can discuss long term where they expect the oral share to stabilize versus the injectable share? That's the first question.

And then the second question is a question on clinician outreach. So Charlie, can you talk about the progress this year? How many new prescribers are adopting ORLADEYO? And what percentage are still in the early days of prescribing? Just remind us our goals for this year and what target you might have for next year? And then last, a quick follow-up. Just can you elaborate a little bit more on the ex U.S. versus U.S. split in Q2?

[Charles Gayer, executive]

Sure. So on the long-term oral share, I mean, ORLADEYO obviously, is the only oral drug on the market. And once a day, you really -- you can't get better than that. So -- and we talked about our path to the $1 billion in 2,000 paid patients in the U.S. And so 2,000 out of over 11,000 total patients, you can imagine ORLADEYO is going to get to at least about 20% share. We'll see what happens with other products in the future, but we're very confident in our overall growth.

As far as prescribers, we continue to see new prescribers coming on board. And we've talked before about our Tier 1 doctors that cover about 50% of the market sort of 500 to 600 doctors there. And then the bigger Tier 2 group in Q2, we got equal number of prescriptions from both of those groups. So very -- continues to be very balanced and we had a very similar number of new prescribers to what we've seen in recent quarters.

As far as kind of doctors in the Tier 1 group, we're now to the point where over 70% of them have prescribed and we keep chipping away at that number. We'll -- we may never get to 100% with them, but we're going to get close. And all the metrics we see as doctors across the board intend to do more.

[Jon Stonehouse, executive]

Charlie, on that 30%, can you talk about how things like more prophy medicines come into the market? And the noise of prophy going up can be an opportunity and the [ peds ] opportunity as well?

[Charles Gayer, executive]

It's a great point, Jon brings up. So we have 2 big opportunities. One, we do expect other competitor injectable products to launch. One may come as soon as the end of this year. And with that, there's just going to be more conversation around switching patients, more treatment options, maybe lower burden treatment injectable products. And so we're going to take advantage of that because we have the product that patients want with an oral once-daily therapy.

And then peds that we intend to file next year. That is an opportunity in itself, but also there's the halo effect from that. There -- it's a genetic disease, their families -- and then there are doctors where this may become their first real experience with ORLADEYO. And starting with the kids and then they maybe move on to the rest of the family. So both of these are opportunities over the next couple of years for us.

[Jon Stonehouse, executive]

Yes. For these KOLs that tell us it's not broken don't fix it. If they've got a pediatric patient on injectable, it's going to be pretty hard for them to not want to switch to an oral. So we think that's a real opportunity to have that conversation with them. And then ex U.S., Charlie?

[Charles Gayer, executive]

Yes. What we see is the same consistent pattern of demand. We see many of the ex U.S. countries moving increasingly towards prophylaxis for market access reasons, they may never get to quite the same levels of the U.S, but we're seeing prophy become the standard of care for patients and ORLADEYO to be growing very strongly and patient retention, too, has been very consistent with what we're seeing in the U.S.

So Europe, Japan, Canada, Eastern Europe, we're starting to launch now with our partners in Latin America, a lot of opportunity and a lot of excitement about ORLADEYO coming to the market.

[Operator]

And the next question comes from Jon Wolleben with JMP Securities.

[Jonathan Wolleben, analyst]

Congrats. Just a couple more for me on the market-sizing updates. I'm assuming in that 8,500 you guys gave us that's including acute prophylactic patients, but wondering if you had any sense of reasons why that other 2,600 or so are not being treated? And then do you have any sense today of what percentage of treatment-naive patients are going to ORLADEYO first?

[Charles Gayer, executive]

Sure, Jon. Of the 8,500, that includes patients that are in HAE-specific medicine. So when we do this analysis, we look at all the prophy products, we also look at all the acute -- the modern prophy products, I should say, so ORLADEYO plus the injectables and then the acute therapies. So that's what's included there. You saw the data where we're attracting 17% of ORLADEYO patients launched to date have come from the treatment naive.

And what that tells us is that treatment-naive group is going to increasingly become a treated group. Some of those patients are probably just becoming aware of their disease or their physicians are starting to become more aware about HAE. And so again, it may never reach 100% of those patients treated, but we expect more and more of them will be treated, and it's a great opportunity to help more patients.

[Jonathan Wolleben, analyst]

But you don't have a sense from market research or what you're seeing in claims like a new patient come in the system is preferring ORLADEYO or TAKHZYRO?

[Charles Gayer, executive]

I knew I was missing one part of your question. We do. ORLADEYO gets -- we have at least 50% of those patients in our market research get ORLADEYO first before other prophylaxis products.

[Operator]

The next question comes from Serge Belanger with Needham & Company.

[Serge Belanger, analyst]

Congrats on another solid or ORLADEYO quarter. First one, given the nice growth we've seen over the first half of 2024, can you tell us a little bit about where you are in terms of market share in the market?

And then maybe for Charlie, regarding the prescriber survey, we've seen a pretty drastic increase in the likelihood of prescribing year-over-year. Just curious what you think drove that increase over such a short period of time? And if I'm not mistaken, you've conducted a survey, I think, every year. Just curious how it is -- how predictive it is for future use and uptake of ORLADEYO?

[Charles Gayer, executive]

Sure. As far as share goes, Serge, I'll point you back to the 2,500 prescriptions we had at the end of last year. Some of those, of course, are repeat patients who had dropped off and come back, but I think that's a pretty good marker roughly of where we are. So depending on how you want to do the math, either of the treated patients or of the total market, we're probably nearing 20% market share, roughly, a little bit below that, but growing very strongly.

And then as far as kind of the indicators of increased prescribing and the physician confidence I think it's what I said in my remarks, they're just -- their experience -- they're learning more about the data, and they're seeing it in their patients. So I think the best way for a physician to learn about this drug is to try it in their patients, and see how well the patients respond.

And that's why of current prescribers now 52% of them say they are extremely likely to prescribe more because they are seeing the response in their patients.

And we do these surveys every quarter. And we always ask physicians, what are you going to treat your patients with over the next 12 months? And what we've seen over the last year is that the drug they see to grow over the next 12 months is ORLADEYO. That is where they see the most growth in the marketplace. And I think it's because of what they're seeing with the results in their patients.

[Operator]

This concludes our question-and-answer session. I would like to turn the conference back over to Jon Stonehouse for any closing remarks.

[Jon Stonehouse, executive]

Yes, I'd just like to wrap it up by saying, again, what I said before, it was absolutely amazing quarter. It's 2 in a row now. The momentum we have, we see no signs of it slowing down. We're now having revenue over $100 million per quarter. And you should ask yourself, why is this happening? It's because this drug really works, right?

When a patient sees control. They have the same kind of control they had with any other prophy medicine they were on before and they get it with a once-daily oral medicine. And that is why we're seeing this great success. And then the last thing I'd say is thanks to the commercial team for just having outstanding performance and continuing to build the momentum in this company. Thank you.

[Operator]

This concludes our question-and-answer session. I would like to thank everybody for joining today's presentation. You may now disconnect.