BioCryst Pharmaceuticals, Inc. (BCRX)
Q2 2022 Earnings Conference Call
August 04, 2022 08:30 AM ET
Company Participants
John Bluth - SVP, IR and Corporate Communications
Jon Stonehouse - CEO
Anthony Doyle - CFO
Dr. Bill Sheridan - CMO
Charlie Gayer - CCO
Dr. Helen Thackray - Chief R&D Officer
Conference Call Participants
Stacy Ku - Cowen and Company
Jon Wolleben - JMP Securities
Chris Raymond - Piper Sandler
Jessica Fye - JPMorgan
Maury Raycroft - Jefferies
Gena Wang - Barclays
Brian Abrahams - RBC Capital Markets
Serge Belanger - Needham & Company
Liisa Bayko - Evercore ISI
Presentation
Operator
Welcome to the BioCryst Second Quarter 2022 Earnings Conference Call. My name is Vanessa and I will be your operator for today’s call. [Operator Instructions]
I will now turn the call over to your host Mr. John Bluth, at BioCryst.
John Bluth
Thanks very much Vanessa. Good morning, and welcome to BioCryst’s second quarter 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; Chief Medical Officer, Dr. Bill Sheridan; and Chief R&D Officer, Dr. Helen Thackray. Following our remarks, we will 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
Thanks, John. The ORLADEYO launch continues to be very strong. Revenue is on track to exceed $250 million this year. New patient starts remain consistently strong now for six quarters in a row. The prescriber base is expanding and deepening. The 96 week data we’ve begun promoting is resonating with our customers. And the switch data shows ORLADEYO is maintaining disease control of decreasing disease burden. While the vast majority of our revenue is still from the U.S., sales from Europe are starting to grow. And all of this is good news for HAE patients.
This is even more exciting when you realize there’s so much more opportunity ahead of us, which leads us to refine our guidance for this year to between $255 million and $265 million and continue to track toward $1 billion at peak.
Why is this important? Having a meaningful product in the market growing quarter-after-quarter with very long IP creates an amazing base to build on. In this challenging financial environment having significant and steady revenue growth is rare and critically important to creating greater value.
Our plan is to repeat this ORLADEYO success with our pipeline molecules for other patients suffering from rare diseases. Few companies can get one successful product to market. But if you’re able to do it again and again, you can compound value. Key elements to getting there or having a strategy to bring therapies forward that patients truly want. And being disciplined by following the data and insights gathered objectively to make informed business decisions about when to invest and when not to. ORLADEYO’s success is a great example of this. Wouldn’t it have been nice back in the early days of the program if clinical trials and market research pointed to a clear and straight path to success, but that’s not how it played out.
There were clear challenges and things that went differently than planned along the way. And we were disciplined in objectively following the data, studying the switch market carefully and quickly leverage those insights to make the investment decisions that ultimately are paying off today with our successful launch.
We use this approach in all our capital allocation decisions including our pipeline. This disciplined approach is especially important in the current environment. We see the complement area and the ability to bring oral drugs to fill large unmet needs for these rare disease patients as a massive opportunity that includes factor D and extends even more broadly to include other targets.
Our immediate decision is to allocate capital in the redeem and renew studies to see if we’re able to achieve our goal of finding a safe and effective dose with BCX9930. It’s the data from the first small group of patients’ enrolled support fiscal, we continue to allocate capital to the 9930 program. If not, we’ll stop its development, but still pursue Factor D inhibitors as we’ve already invested in next generation backups and molecules that we hope will be improvements.
With the partial clinical hold now removed preparations to restart enrollment have begun. And Helen will share more with you on what we know now and how we plan to proceed. We have a successful rare disease launch with ORLADEYO growing into a global blockbuster. We have an exciting pipeline of compounds some you know about and some you don’t yet.
And lastly, we have substantial capital to make thoughtful capital allocation decisions. This is a unique and very good spot to be in the current environment and that brings me back to where I started the tremendous market success of ORLADEYO. The steady and consistent revenue growth, discipline in objective decision making on capital allocation and alternative financing sources like the additional debt from a theorem we recently drew down are the things that give us confidence we can repeat the ORLADEYO success with other molecules and create much greater value in the process.
Now I’ll turn the call over to Charlie to share additional details on another strong quarter of growth of ORLADEYO. Charlie?
Charlie Gayer
Thanks, Jon. The consistent pattern of patient growth that we’ve seen since launch continued without interruption in the second quarter. New Patient prescriptions in Q2 are the best since the first quarter of the launch, driven by continued broadening and deepening of the ORLADEYO prescriber base. There is no sign this launch is slowing. Our market research with HAE treaters predicted this expansion and the 96 week data that we started promoting late last year is convincing physicians to prescribe.
When they see the sustained median monthly attack rate of zero they know that their patients can expect great efficacy. When they see patients doing really well on ORLADEYO in the real world in particular, those patients who switched after being controlled on injectable prophylaxis, they were encouraged to increase prescribing. Our prescriber data in Q2 reflect this pattern.
We added the most first time prescribers since the third quarter of last year. And we also had an identical number of repeat prescribers. We saw an uptick in prescribing among the top 500 physicians that treat 50% of HAE patients. 60% of those tier one physicians have now prescribed ORLADEYO and they accounted for two thirds of new prescriptions in the quarter.
Our source of business is also very balanced with overall patient potential. There are roughly 120 physicians in the top three deciles, accounting for 30% of the HAE market opportunity. And they prescribed 32% of the ORLADEYO prescriptions in Q2. Roughly 1,400 physicians represent the next 40% of the opportunity, and that group accounted for 48% of prescriptions.
We also saw an improvement in patient retention although it is too soon to call this a trend we have the fewest number of discontinuation since Q3 of last year, even as the overall number of patients on ORLADEYO has grown substantially. Our metrics on access and reimbursement which were already good, also continued to improve. The median time to shipment of reimburse product for a new prescription is now under three weeks as our team helps patients move quickly through the prior authorizations. Healthcare providers worry about the burdens of the access process for HAE treatments. So the success of our patients service model adds to their confidence in prescribing ORLADEYO.
We made more progress toward the globalization of ORLADEYO in Q2 with regulatory approvals in Canada and Switzerland, and final price agreements in Germany, France as well as Switzerland. We also entered a commercial distribution agreement with Pint Pharma for Latin America and we expect to file for market authorization and multiple Latin American countries before the end of 2022. While ex-U.S. contribution to 2022 sales will be small the progress we are seeing in Europe and other regions gives us confidence that ex-U.S. sales for ORLADEYO will reach at least $200 million at peak.
The prescribing dynamics and the patient trends that we saw in Q2 confirmed to us that we are still in the early stages of the ORLADEYO launch trajectory. The trends that we see tell us that ORLADEYO on track not only for between $255 million and $265 million in sales in 2022, but also future market leadership and a billion dollars in peak sales.
Now I’d like to turn the call over to Anthony.
Anthony Doyle
Thanks, Charlie. ORLADEYO revenue performance for Q2 was really strong and takes our trailing 12 month revenue to just short of $200 million. With the consistency of new patient growth in the U.S. and continued expansion globally we’re really well-positioned to achieve our updated revenue guidance of $255 million to $265 million for 2022 and on from there to peak sale to the billion dollars. 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.
Revenue for the quarter was $65.5 million, of which $65.2 million came from net sales of ORLADEYO. We had around $2.2 million of non-repeating reimbursement related accrual releases in the quarter and so ORLADEYO on net revenue specifically related to Q2 with $63 million. Having seen Q1 gross to net impacted by reauthorizations, copay assistance, resets and the government doughnut hole, Q2 reimbursement rates and gross and at adjustments have normalized and should continue at current rates through year end.
Operating expenses, not including non cash stock compensation for the quarter was $90.4 million. This was lower than we previously forecasted as the team worked hard to manage costs during the 9930 enrollment whole period. With the program now moving forward, we’ve lowered our OpEx forecast for 2022 to $390 million to $400 million.
Cash at the end of the quarter was at $490 million having achieved and maintain the required revenue thresholds to draw the additional 75 million debt tranches from a cerium Pro form of cash is at approximately $492 million. We have always been and will continue to be responsible and disciplined allocators of capital. This is especially true as we recommence enrollment, 9930 program. We have taken into consideration the delay to the program applied to reduce probability of success and reduce their assumptions for peak penetration. Despite that, there’s still significant value potential to support investments in the program.
There are numerous markets that we can go into with 9930, not just PNH. These markets are big, especially in renal indications. And this is a drug that patients want all of that results in a revenue potential for 9930 that is larger than that of ORLADEYO. Our intent is to progress as quickly as possible, limit the additional investment and get to the point where we have confidence that we have a safe and effective drug. If we can achieve this, then we will continue to invest in moving the program forward. If we cannot, then we will terminate the program and allocate capital elsewhere. This data driven objective unemotional approach has been a key factor in the successful launch of ORLADEYO and will continue to guide us in all of the programs that we have going forward.
Now I’ll pass it over to Helen.
Dr. Helen Thackray
Thanks, Anthony. As we announced today, the FDA has lifted their partial clinical hold on the BCX9930 program, and our pivotal trials and PNH can resume enrollment along with our proof of concept trial in renal indications. This is an important step forward toward our goal of bringing a safe and effective Factor D inhibitor to patients with PNH and complement mediated renal diseases. We will reinitiate enrollment using a step up approach and a dose level of 400 milligrams twice daily together with encouraging hydration, and more frequent safety testing for the first few months in each patient.
After review of the data and investigating the elevations in serum creatinine, we reported in April, we’ve arrived with a hypothesis for the mechanism contributing to these observations and our proposal for how to address it. The hypothesis is that crystals are forming in the kidney when the concentration of the drug is highest in the urine, and that this can be mitigated by lowering drug levels in the urine. We will test this by lowering the dose from 500 milligrams twice daily to 400 milligrams twice daily and encouraging adequate fluid intake to achieve dilution of the drug as it is excreted in the kidney. If we are correct in our hypothesis, and these steps successfully addressed the problem, this will mitigate the risk of elevated serum creatinine in patients receiving BCX9930.
The evidence in support of this hypothesis comes from clinical observations and laboratory studies. As we shared in May, the clinical evidence suggested that the serum creatinine elevations occurred only at the 500 milligram dose level, and were likely dose related. In addition, our recent clinical pharmacology studies have shown that a large fraction of the administered dose of BCX9930 is excreted by the kidney. Importantly, new laboratory studies have found BCX9930 drug solubility is lowered over the typical pH range of human urine. And recent non-clinical studies have also demonstrated dose related crystal deposition in the renal tract and kidneys in animals.
Understanding that suggests mechanism contributing to the rise in serum creatinine, it is likely to be a physical one where crystals form in the urine, in the kidney when you’re in concentration of the drug reaches a threshold level. The crystals cause an inflammatory response with resulting damage to the kidney cells. This would explain how kidney function is affected and why a rise in serum creatinine is observed with BCX9930 at 500 milligrams.
It could further explain why it is happening only in some patients and at the 500 milligram dose level when inter renal drug levels exceed a threshold for crystal formation. This mechanism of injury is avoidable. We believe that the keys to avoiding risk of adverse kidney effects are to reduce the load of drug excretion by lowering the dose and to maintain more dilute urine to further lower the concentration of excreted drug by encouraging adequate fluid intake, especially at the time of drug administration.
That dose reduction together with the dilution effect of hydration is designed to maintain adequate levels of the drugs circulating in the blood for efficacy while reducing the concentration on elimination in the kidney to avoid crystal formation. Of course, we also need to maintain strong clinical efficacy. As a reminder, the data from our Phase 1 PNH program supports studying 400 milligrams twice daily.
When C5 inhibitor naive patients were taking this dose, 400 milligrams in the Phase 1 program, the hemoglobin rose from baseline by a robust amount, a mean of 4.3 grams per deciliter, and no transfusions were required. This clinical observation was consistent with our PK/PD work, showing that 400 milligrams twice daily provided plasma levels above the exposure needed to achieve near complete inhibition of the alternative pathway of complement. Given that evidence, we believe that 400 milligrams twice daily will achieve similar efficacy results to those we saw in phase 1.
So what comes next, if we are correct in our hypothesis, and if the steps we are taking are the right ones to resolve the elevation in serum creatinine, while maintaining strong clinical efficacy, we will be able to confirm this in the clinic. Our next steps are to lower the dose for patients already on study. While in parallel, we reopen the studies to enrollment. To do this, we will proceed with regulatory submissions for the amended protocols and then REDEEM clinical trials. We’ve included simple hydration instructions for all patients. And for new patients we’ve included a revised regimen to get to the 400 milligram dose level with a short initial step up in dose. We are also amending the RENEW trial with similar measures and initiating the steps to reopen to enrollment at the 400 milligram dose in that trial.
In terms of testing our hypothesis, we will assess patients in the first month of reopening enrollment in the REDEEM and RENEW trials and we will observe patient outcomes closely to determine if the data on safety 400 milligrams supports continuing to invest through to completion of the pivotal studies. Provided we can recruit patients in a timely manner and the initial data are supportive of safety and efficacy, we will proceed. If the data are not supportive, we will discontinue the 9930 program and redirect our efforts and investment elsewhere in our pipeline.
So how will we know this? As we resumed enrollment at 400 milligrams, we’ll look for an absence of the early rise in serum creatinine in new patients enrolling in the study. You will recall that over the first few months of enrollment and REDEEM 1 and REDEEM 2 and in about 1/3 of the first 15 patients, we saw a rapid rise in serum creatinine at 500 milligrams. As we enroll patients at 400 milligrams this will give us a good basis for comparison to inform our next step.
Look at it like this. If about the same small number of patients are treated without similar observations this will build confidence that the hypothesis is correct, and the protocol adjustments are sufficient to address it. By monitoring for serum creatinine at more frequent intervals in the first three months, we will gather the information we need to determine if our hypothesis is correct and if our revised amendments sufficiently resolve the problem.
On an individual patient, more frequent monitoring will allow us to identify any changes in the near term and react swiftly if warranted, both for each individual safety on trial and for any appropriate decision on continuing the program.
It’s clear to us that the need for better treatment options in these diseases is significant. Throughout our investigation, we have received unwavering encouragement from our investigators and patient organizations in both the hematology and nephrology communities to find a path forward for BCX9930 if there is one. We are pleased that the FDA has removed partial clinical hold following their review of our data, our investigation findings and our proposed protocol adjustments.
Because of this high unmet need and PNH and other complement mediated diseases and because we believe making a limited additional investment now to test this hypothesis is warranted by the potential value if the program is successful we continue to pursue our goal of bringing a safe and effective Factor D inhibitor to the market for these patients. We are working hard to achieve this goal. And we will make the decisions on where to invest in our pipeline based on sound evidence and where we can create the most value.
Now I’ll hand the call back to John.
John Bluth
Thanks Helen. Let me conclude by summarizing where we are. The ORLADEYO launched through six quarters continues to be strong with no signs of slowing down and we are on our way here to global peak sales of $1 billion. We have a testable hypothesis with 9930 that we believe we can answer in relatively short order and if 400 milligrams BID is a safe and effective dose, we have an asset, potentially more valuable than ORLADEYO. If not, we move on to the rest of our pipeline to find the next ORLADEYO.
We have a very solid balance sheet and when the capital markets are challenging, like they have been for a while now we can access other sources of capital. Add this all up and you can see we are creating meaningful value now and we have the potential for much greater value in the future.
That concludes our remarks and we will now open up the call to your questions.
Question-and-Answer Session
Operator
Thank you. We will now begin our question and answer session. [Operator Instructions] We have our first question from Stacy Ku with Cowen and Company.
Stacy Ku
Hi, all, thanks so much for taking our questions and congratulations on ORLADEYO quarter. So we have a few questions. First, on the 9930 update. Can you speak about the patients that have stayed on the REDEEM trials? Are there any safety measures that are being monitored any updates there? Sounds like they are on 500 milligrams and that will be adjusted to 400. That’s the first question on those patients and then for the second. Can you talk about kind of the FDA decision a little bit earlier than expected? So should we look into that as any read through kind of clearly an overhang for the street? So any details would be appreciated there. Thank you.
Jon Stonehouse
So, Helen, you want to take the first one. I’ll pick the second one.
Helen Thackray
Sure. Thanks for the question. So with regard to patients on REDEEM trials, we have continued to monitor them. Patients who remain on drugs are doing so because per the partial clinical hold, they were continuing to derive benefit. They continue on drug, their results have supported that. And we’re reducing the dose in all patients.
Jon Stonehouse
And then on the FDA question, we said the end of the third quarter, because we didn’t know how many rounds we’d go back and forth with the FDA. And when we sent in the complete response to their whole they reviewed it and we got off clinical hold. So we got off faster than we originally planned.
Stacy Ku
All right, that’s very helpful. Thank you.
Operator
Thank you. We have our next question from Jon Wolleben with JMP Securities.
Jon Wolleben
Hey, good morning, and thanks for all the color on the 9930 update. Just wanted to ask previously discussed two different patterns of the creatinine elevations some patients seeing it early and then some developing over time. These mitigation steps in the effects the ladder but wondering, he talked about the potential risk cropping up over time on some patients as they stay on 9930 long term.
Jon Stonehouse
Let me start and then you and Bill can jump in. So I think the important thing is a small number of patients like we saw in the early start of the enrollment of the REDEEM study is going to give us a sense of the first pattern which was that acute rise and those same patients we’re going to continue to track over time. And we’ll get a sense of what happens over time with the same small group of patients. So I think we get the benefit from both patterns with this early group of patients.
Helen Thackray
And I can answer on the other point on the early rise in this low trend. We think this is a threshold effect. We think it’s the threshold of the drug concentration in the urine. That could explain both the early rise findings and the slow later findings. We expect to be able to answer each of those questions in the first small group of patients who are enrolled.
Jon Wolleben
That’s helpful and then maybe a couple follow ups. Helen, you discussed a few different procedural steps to get picked new patients in. I am wondering when do you think you could start dosing new patients in REDEEM and RENEW? And then also when you’re thinking about this early evaluation what is the bar that’s acceptable? Do you have to see complete absence of serum creatinine or is there any discussion with FDA about what can you see that’s tolerable and what isn’t tolerable here?
Jon Stonehouse
So maybe in that second one, the stopping rule and the first one is pretty straightforward.
Helen Thackray
Yes, so we have some work to do initially, which is to get the protocols up and running. We have to submit to countries and sites that will take a few months and then we will be enrolling from there. We expect that within the first few months of experience with the first trial patients will have the opportunity to see data. So this is an incremental approach first is get to the readiness for startup then get to enrollment then get to the data. And in terms of what we’re looking for, then we think that this is the threshold effect. As I said, the goal is to avoid that. And so what we’re looking for is to patients to be dosed at the 400 milligram dose level, and for us to be seeing in those new patients that we’re not observing these findings.
Jon Stonehouse
Yes. If we have serum creatinine and major increases in serum creatinine and then we don’t have a drug that’s safe and effective, right. So it’s pretty straightforward. And on the first point, we’re going to go as fast as we can. It’s hard to predict how quickly that’ll happen. But we’re going to go as fast as we can.
Jon Wolleben
I’ll jump back in the queue. Thanks for taking the questions.
Operator
We have our next question from Chris Raymond with Piper Sandler.
Chris Raymond
Yes, thanks. Two questions, I guess first on 9930. Maybe could you provide a little bit more color on the sort of hydration protocol, I guess you’re describing. I’m just trying to understand what specifically you submitted to FDA in terms of what patients need to do. Is it more of the hydration or the lower dose I guess that you’re hypothesizing can alleviate this issue?
And maybe just give us a sense of how this sort of translates into the real world if in fact, you keep going with this with this hydration protocol, and it’s approved, and then there’s this requirement for patients to hydrate.
And then the second question on ORLADEYO, we’ve done some KOL checks. I’m kind of curious what you guys are seeing in the larger market. The feedback we’ve gotten is that overall prophy share is relatively growing steadily, but share of new patients is really where the bolus of uses like 80% or more of new patients, at least from one of our KOLs. So I guess I’m just kind of curious, what are you seeing in the broader market? And if you’re seeing similar sort of proportion there, what kind of lag you anticipate before this really starts to accelerate total share? Thanks.
Jon Stonehouse
Do you want to take the first one on hydration?
Helen Thackray
Yes. So 9930 hydration protocol is actually really simple. It’s simply to encourage hydration while on the drugs that could be as simple as taking the drug with a glass of water. We’ve not prescribed specifically what it should be. But it’s encouraging hydration. The reasoning behind that is that we’re taking a two pronged approach to be able to get the urine concentration below the threshold for formation of any crystals. And that’s both with the dose reduced within the effective dosing range and the addition of hydration in order to get to that sustained level below the threshold for crystal formation.
In terms of where this would go in the sort of next, if you use this in the real world, it’s really quite simple. This is as simple as take your medicine with a glass of water. And so we think that this is very achievable.
Jon Stonehouse
Great, Charlie, you want to take the ORLADEYO?
Charlie Gayer
Hey Chris. Thanks for the question. So first of all, overall 50%, about 50% of the patients that are on ORLADEYO have switched from another prophylaxis product and that’s really in proportion to what we think is the market share. So about half of those switchers prophy switchers are coming from TAKHZYRO then Haegarda and so on. As you know, I talked about the prescriber base, we’ve got a really big prescriber base. And so I think we’re still early in this process of getting all the different KOLs to fully understand this, and I think in the future, they will switch more patients.
But across the overall market, there’s been a lot of switching. And as more and more doctors get familiar with our data and see the real world efficacy that those prophy switchers are having, I expect that the trend will continue.
Operator
We have our next question from Jessica Fye with JPMorgan.
Jessica Fye
Good morning. Thanks for taking my questions. So a couple more for you on 9930, when you talk about a reasonable timeframe, and a relatively small number of patients needed to find a safe and effective dose can you just elaborate on how you define two things. First, is a reasonable timeframe the three months you talked about in prepared remarks and is that three months from today or is that once you get three months of follow-up on a small number of patients, and it could take a few months to spool up enrollment again?
And then second, how do you define a small number of patients? Is that a dozen? A couple dozen? Just trying to figure out when an investor will have more clarity here.
Jon Stonehouse
Yes. So I think it’s important to look at what we saw in the study that caused us to stop. So it was about 15 patients, roughly in enrollment and the REDEEM studies that that we saw this effect. And so we think that a similar number is roughly what will give us confidence that we’re not seeing the effect or we are and the timeframe for that, as Helen said could take some months to get the revised protocols. These are major amendments, and so you got to go to the regulatory authorities. And then it took about two months to see the effect in these patients.
So once we got it up and running, and we’re enrolling patients, it’ll be a couple of months before we see, we feel like we’re in a position where we know what we’re seeing. So I hope that gives you a little bit more framing. So it’s really hard to predict just because it takes time to get these things approved, and, and then start enrollment. But we’re going to work as fast as we can. And we’ll keep you updated along the way.
Jessica Fye
Got it. And I appreciate the kind of deliberate approach here. And I can understand how a small number of patients can rule in a safety issue. But how do you get comfortable that a small number of patients can rule out a safety issue?
Jon Stonehouse
Yes, maybe I’ll start in the new and Bill can jump in. The hypothesis is based on the data we’ve gathered today which is a combination of the clinical data and what we saw at 400 and what we saw at 500 and then what we saw in [Indiscernible], and what we saw in laboratory tests and some recent animal studies. And so, we believe it’s the threshold effect that causes the drug to go out of solution and causes the clogging of these tubules. And so we think that if we don’t see these elevations, we won’t, it’s not something that will linger on over time. It’s not, this drug doesn’t accumulate.
So it’s not something that will happen over time. It’s not an exposure issue. It’s a threshold issue. So that’s why we think the small number of patients and the early phase of the study will give us much more confidence. Helen or Bill anything else you want to say?
Helen Thackray
I would only add the findings in that first group of patients that for which we paused enrollment, those are pretty definitive. They were pretty early. And I think if we don’t see that in the first group that’s about the same size, as you said. It would give us increasing confidence. This is going to be an incremental approach as well. We need that first step. We need to see that and then we’ll continue to follow them and add more patients.
Bill Sheridan
Yes. The only thing I will add is it gives you confidence to complete enrollment in the studies.
Jon Stonehouse
Yes, that’s right.
Operator
Thank you. Our next question is from Maury Raycroft with Jefferies.
Maury Raycrofts
Hi, thanks for taking my question. For ORLADEYO, can you elaborate more on what the ideal patient to switch and the ideal patients to benefit from ORLADEYO? I guess are there some observations that you’re seeing from the front line that you can talk about?
Charlie Gayer
Yes Maury good question. And, yes, we’re starting to get an increasing amount of evidence about the ideal patient. And it really is patients who were already well controlled on another prophy drug. If they had a very low attack rate coming in, most of those patients tend to stay at the same low attack rate on ORLADEYO and so I think as more and more physicians start seeing that and as more and more patients started experiencing that that’s where we’re going to see more the trend of switching continuing and maybe even increasing.
Jon Stonehouse
And Charlie, when you say low attack rate coming in, you mean on their prophy.
Charlie Gayer
On their, exactly on their existing prophy therapy, and then they switch and keep the same low attack rate on ORLADEYO.
Maury Raycrofts
Got it. And thanks for providing all of the detail on 9930 as well. I’m just wondering for the actual molecule. Do you have an understanding of why it’s crystallizing? Is that something that is relevant as so why the molecule is actually crystallizing?
Helen Thackray
Yes, I can take that. So we have since making these observations as said in the remarks, we’ve done further work in the laboratory and we’ve been able to establish the solubility level. The pH range in the urine. It’s simple crystal formation as a result of the molecules chemistry, so there’s nothing really special about it. But now that we know that we know what to look for.
Operator
Thank you. [Operator Instructions] We have our next question from Gena Wang at Barclays.
Gena Wang
Thank you very much for taking my questions. I have a few regarding the ORLADEYO and so I hope I did not miss it. Just wondering, have you mentioned the patient retention rate, would they still maintain at a 70%? And regarding the new patient percentage of patient that switch from other prophy, what was the number there, was this to like 50%?
And then quickly on the pricing I know you finalize in Germany, France and Switzerland. What are the comparison the price compared to the U.S. price? And sorry, one last question, regarding Factor D, how much initial capital allocation will you put for the program?
Charlie Gayer
So on patient retention, what I did note is that we had a decrease in discontinuations in Q2. So retention of too soon to call it a trend, but it appears to be getting better. It’s been a real focus of the team, particularly in improving retention early in therapy so that patients don’t give up too early. The overall retention rates since launch, like I said before was in the mid 60% retention since launch, it’s similar to that. But what’s really important now is we see some signs that this is improving.
And as far as the overall switch rate, I think I just mentioned a minute ago, about 50% of the patients have switched from other prophy. And then the other 50% is mostly switching from acute only and then some patients who are naive to therapy starting ORLADEYO as their first drug.
Jon Stonehouse
Yes. I think part of your question was retention. And those folks it’s actually better in…
Charlie Gayer
That was the other parts. So I’ve mentioned this in previous calls that the retention of people switching from injectable prophy at six months for TAKHZYRO and Haegarda [Indiscernible] is in the high 70%. And that’s based on the fact that they were well controlled before and they stay, most of those patients stay well controlled on ORLADEYO.
And then you had a question about EU pricing. So our German list price is about 156,000 Euros. The Swiss price is a little bit higher than that. So you get a sense for how that compares to the U.S. were whack pricing is $499,000.
Jon Stonehouse
And then Anthony, you want to take the capital allocation question?
Anthony Doyle
Yes. So from a capital allocation perspective, it will depend on how quickly we can move through the trials, our intent is to move as quickly as possible. Helen talked about it being incremental in terms of how we move forward with the program. One thing I will say is, we’ve talked about it being a small number of patients that we need at the start. We’ve also said in the guidance that we’ve reduced our OpEx guidance down to 390 million to 400 million for the year.
So that in combination with the revenue increase in the guidance means from a net cash burn perspective we’re definitely in a better spot now than we were previously. So will be absolutely responsible and smart in terms of how we invest that capital. It is the right investment in capital at this point in time given the potential returns.
Operator
We have our next question from Brian Abrahams with RBC Capital Markets.
Brian Abrahams
Good morning. Thanks for taking my questions and congratulations on the continued strong ORLADEYO launch. A few for me, I guess, on 9930 are there mechanistically different considerations with regards to this crystal formation for PNH patients versus those with underlying kidney disease?
Secondly, on the interim assessment that you’re going to be doing, will efficacy be a part of that and will the FDA have any requirements that they’ll need to sign off on before the trial is expanded out?
And then lastly, on ORLADEYO it sounds like you’re reiterating your billion dollar peak sales estimate. I’m just wondering if there’s any evolution in the parameters that form your confidence around that it sounds like the U.S., ex-U.S. break down is similar to what you would expected before, but just wondering if the improving retention, new patient starts degree of overall market growth, how those factors are evolving to continue to shape that goal. Thanks.
Jon Stonehouse
Helen you want to take the 9930? And then Charlie can take the ORLADEYO?
Helen Thackray
Yes. So the first question was, is there any mechanistic difference in the patients with different diseases. And we don’t think so. And the hypothesis is, crystals forming when there’s a high concentration of the drug excreted in the urine. That is a drug that’s independent of disease. So once we have solved this for dose that is safe and effective in one disease, we would expect that to be relevant in all diseases.
Your second question was in terms of what we are assessing on an interim basis in the study. This is a simple safety assessment. It’s simple observation if we see continued episodes of rising creatinine in patients being dosed at 400 milligrams, and we’ll know that we’re seeing it if we’re not, then we won’t be. And that’s the extent of the interim view.
Charlie Gayer
Yes. And this question too, was around the FDA and efficacy, there were no requirements by the FDA. They are always looking at a benefit risk. And clearly, they see some benefit in keeping the patients on this study and us continuing the study. But from an efficacy perspective if we have breakthrough hemolysis we’ll see that and we’re evaluating whether the DMC can look at the blinded data or un-blinded data as well from an efficacy perspective. So we’re concerned about both, Brian and those we said before, the goal is a safe and effective drug.
Jon Stonehouse
Brian as far as the billion dollars, nothing significant has changed. As you know, we do a lot of market research, a lot of planning. And as we see the real world evidence, the real world results matching up what we expected, we gain even more confidence and reiterate. So what we’re seeing in Europe, that early uptake, the pricing that we’ve been able to achieve is in line with our expectations. And so that gives us great confidence in that getting to at least 200 million in the rest of the world.
And then the real world evidence that I’ve talked about coming out of patients who are switching to ORLADEYO in the U.S. and the fact that most of those patients are staying on drugs and having a great experience gives us that much more confidence. And then what I said about our prescriber base expanding, all of this just gives us more confidence in where this drug is headed.
Charlie Gayer
And quarter after quarter, it keeps getting better. We’re growing sales. We’re expanding prescribing. We’re getting more into the funnel in terms of new patients. Our confidence goes up every single quarter. there is no sign of slowing down.
Brian Abrahams
It’s really helpful. Thank you guys.
Operator
We have our next question. Our next question comes from Serge Belanger with Needham & Company.
Serge Belanger
Hi, good morning. I guess one on 9930 to start off. Did I hear correctly that you are evaluating some of the backup molecules to 9930? And if I did hear correctly how close are they to being ready for clinical evaluation?
And then on ORLADEYO a couple for Charlie. Can you talk about where you are with market share now and in terms of new patient add cadence of progress in the second quarter and maybe whether you expect some seasonality impacts on that cadence? Thank you.
Jon Stonehouse
So I’ll take the backup one and Charlie and then you take the ORLADEYO new patients. Yes, we’re always working on backups and we didn’t slow down. We’ve always put full court advance, as I said in the remarks that we’re investing fully in those and so I can’t tell you yet when it’s ready to share more broadly, but there are multiple backups and as we have more data, we’ll share that with you.
And I think the other piece is, we worked to have improved molecules as well and you saw that with the move from [Indiscernible] to ORLADEYO. And so in this program we’re trying to do the same whether or not we’ll be successful is to be determined but full speed ahead on the backups.
Charlie Gayer
And then Serge as far as market share. We’ve shared some of our market research in the past to think most recently some data from earlier this year the survey showed ORLADEYO share of about 12%. That was probably a little ahead of where we actually were in the market at the time. But then we’ve grown since then. And physicians see, our market research, see this becoming their most prescribed drug in the future.
And as we’ve said, before all we need is 25% to 30% market share in the U.S. to get to about $750 million - $800 million towards that billion dollars of peak sales. So it’s growing all the time, we’re doing well.
And then as far as the new patient cadence, I mentioned in the remarks that we had the most new patient prescriptions in Q2 since the very first quarter of the launch and that’s really significant now six quarters in. No signs of slowing down. And as far as the summer slowdown, any differences there we’ll see. We’ll talk about that after Q3 but we ended Q2 in June, really strongly. So I feel good about where we are.
Operator
We have our final question from Liisa Bayko with Evercore ISI.
Liisa Bayko
Hi, thanks for taking the question. I understand what you’re saying about the threshold effect for 9930. Yet you did have some patients that had these elevations and some that didn’t. Any ability to decipher what that is and what’s your threshold, I know you saw it in 15 patients like if you see one case, is that enough to stop? What’s your threshold for like seeing cases, as you go into this next phase now?
Helen Thackray
I can take questions. So on the threshold. Yes, we have seen this in some patients not all. We do think this is a threshold effect. What that means is that in some patients, under some circumstances, crystals could be forming. And we’re pretty close to the edge of that threshold with the 500 milligram dose. That’s what we infer. And that means that with the two pronged approach, and that’s part of why we’re taking that two pronged approach of reducing the dose and hydration, we could see that we get below the threshold for all patients at all the time. And that’s the goal is to avoid this. So this is hypothesis. We’re still working on this. We need to observe in the clinical setting if we’ve addressed this with 400. But that’s why we think it’s happening, it’s just sporadically occurring, because we’re close to the threshold some of the time, but not all the time.
Jon Stonehouse
And then the stopping rule and what’s the, I think that’s important for people to know.
Helen Thackray
Yes. And the question is one case enough. So what we think is that there are multiple things that can also occur in patients with these diseases that can cause rise in serum creatinine. We want to make sure that we are assessing any rise in serum creatinine in the context of where it what’s happening with the patient and if it is likely to be related to the drag or something else. So we’re setting these, we’ll review them together with our DMC. We have a stopping rule in the studies that is, if we see three events that are serious events and that are considered to be related to the drug. That’s the point at which we would stop the study.
Liisa Bayko
So it’s three cases. And then just this notion of inferring like, what makes you believe that 400 is sort of below that threshold?
Helen Thackray
So it’s a hypothesis, and it’s based on what we see at this point. In the data we have not observed this at 400 milligrams, and we do have every patient in the phase one went through the 400 milligram stage of dosing.
Jon Stonehouse
It’s a drug concentration thing, if you have less drug and you have more hydration, less chance of having to go out of solution. So there’s logic there too.
Liisa Bayko
And then I’m sorry, I may have missed it. But did you break down sales like U.S., Japan, rest of world or could you do that?
Jon Stonehouse
We have not broken that out yet, Liisa.
Charlie Gayer
And the reason we haven’t is, the majority of it is U.S. So the other stuff isn’t significant enough to report, but it is growing. I mean, when I said that in the remarks that it’s nice to see you’re growing and that’s not surprising, because now we’ve got pricing now we’ve got promotion now patients are getting on therapy. So over time we will break it out, but at this point, it’s vast, vast majorities U.S.
Liisa Bayko
And then one quick question. I’ve been getting questions from clients lately about the types of patients who stay on ORLADEYO for longer than six months? And is there any relationship between sort of severity of disease and response? So if you could just kind of talk about the kinds of patients who tend to be more sticky and then related question on severity in response to ORLADEYO? Thank you.
Charlie Gayer
Yes, the type of patient that tends to be the most sticky are again those patients who were well controlled on another drug and then switched over the ORLADEYO and remain well controlled. And so the fact that they were on prophylaxis prior, suggested they needed their attacks controlled. And then they maintain that same rate on ORLADEYO.
Jon Stonehouse
Yes. This idea of attack severity or frequency of attack, people control their disease now. So that’s like a, that’s an old way of looking at it. Now, the way you should look at it is where are we getting the business. We’re getting it from people that are controlled on their injectable therapy, but don’t want the burden of therapy to the injectable therapy. Those are the people we’re getting, and that’ll continue to grow. And we’ll get more and more share of that.
Operator
Thank you. This concludes our question and answer session. I will now turn the call over to Mr. Stonehouse for closing remarks.
Jon Stonehouse
Yes, thank you. Something I’ve learned and I think we’ve learned as a company over many years of working on many, many projects, is the importance of objectivity and following the evidence and the data in our decision making whether it’s clinical data that we’re looking at to advance a program or market data, do we have the right profile that will be competitive in the marketplace, if you go into it, wanting to see a certain thing, you’re not going to be objective, and you could make the wrong decision.
We don’t do that at BioCryst, we look at the evidence and we make our decisions based on what we see. And I think as a result of that, we’re starting to create greater value and have more success. And ORLADEYO is the case study for that. So if you’re not familiar with our thinking we encourage you to get to know us better and we can share with you and listen, it’s not the only part that’s important in success. People, good science is also but the decision making on this stuff and the objectivity is critical. And we think it affects value tremendously. So thanks for your interest in our company and have a great day.
Operator
Thank you. Ladies and gentlemen, this concludes our conference. Thank you for participating. You may now disconnect.
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BioCryst Pharmaceuticals, Inc. (BCRX) CEO Jon Stonehouse on Q2 Results - Earnings Call Transcript