We provide a research subscription service with a free trial and cancel anytime. Try us out to see if we’re a good fit for your needs. See our service, plans and pricing, customer reviews and more by clicking here.
- Read the press release here
- $244.4 million cash and equivalents as of March 31, 2021 with a $75 million available from an existing credit facility
- Primary endpoint for oral BCX9930 PNH trials will be change in baseline hemoglobin, trials expected to begin 2H 2021
- $10.9 million Orladeyo revenue mainly driven by “new patients who switched to ORLADEYO from either injectable/infused prophylactic medications or from acute-only treatment. The remainder came from patients transitioning from clinical trials and the company’s early access program”
John Bluth (IR): Good morning and welcome to Biocryst first quarter 2021 corporate update and financial results conference call. Today’s press release is available on our website preferences. Meeting with me today are CEO john stone house CFO Anthony Doyle, Chief Commercial Officer Charlie Guyer, Chief Medical Officer, Dr. Bill Sheridan, Chief Business Officer Megan zinfi, and Chief r&d officer Dr. Helen dag. 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 audit and forward looking financial information as well as the company’s future performance or achievements. These statements are subject to known and unknown risks, uncertainties which may cause our actual results performance or achievements to be materially different from any future results in 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 artist factors, please refer to the company’s document is filed with the Securities and Exchange Commission, but it can be accessed on our website. I’d now like to turn the call over to john Stonehouse.
John Stonehouse (CEO): Thanks, john, I couldn’t be more excited to have our first earnings call with revenue from a Biocryst launch product. This is the latest that it is that our company is going through a major transformation. sales were very encouraging in q1, especially considering this is our first quarter of a launch in order to do this is a direct result of focus execution on our plan by the Biocryst team. And a desire to build a great company that can discover, develop and now successfully commercialize oral medicines for patients suffering from rare diseases. Very few companies can do all three.
The launch is off to a great start because we have a great drug it works patients are experiencing meaningful reductions in their attacks. And they can achieve this by taking one capsule once a day. This is meeting the patient switches from injectable prophy on demand therapy to exactly what we saw our market research and clinical trials. And it’s already playing out the marketplace.
Great drugs don’t sell themselves. We also have a fantastic team. Charlie and Alan Hodge at USGM have assembled an experienced team. But more importantly, they’re working together working through challenges and obstacles like COVID and achieving great results. We couldn’t be more pleased with the start and the good news. We’re just getting going with so many more patients to reach in the US.
while the US is the largest market we now have approval and other major territories around the world. Our partner Torii is launching in Japan and we recently received approval in the EU. The same plane investments were made here to the launch ramp will take longer as these are different markets from the US. But we expect these countries to contribute over time to our goal of achieving $500 million plus in global peak sales.
And finally, our pipeline is full with the opportunity we have with our oral factor d inhibitor BC9930. For patients suffering from many different complement mediated rare diseases, pain, independent pivotal studies and PNH. And proof of concept in the phrase indications, we will apply all the learnings of our ag program and build off that success through 99. Or you can market to create even greater value as a company that discovers develops, and commercializes multiple oral drugs for patients suffering from rare diseases. Now I’ll turn the call over to Charlie to go over more details about our early launch success. Charlie.
Charlie: Thanks, john. The Orladeyo launch is off to a great start. We’re pleased but not surprised. We had a great drug that patients want because they’re tired of the physical, psychological and logistical burdens and injectable therapies. Physicians also tell us they’re confident and prescribing roadeo for a broad range of patients with a long term data on attack reduction, safety and tolerability. Here’s what we’re seeing so far. In a very competitive market patients are switching to Orladeyo, over half the patients starting or starting for the first time are switching from an injectable prophy. The rest are switching from an acute treatment only now they had an oral once daily prophy option. In fact, the majority of patients on Orladeyo by the end of q1 were those who switched from other products. The rest were patients transitioning from our clinical trials in Early Access Program.
The prescriber base also continues to expand. former clinical trial investigators account accounted for the minority of Orladeyo prescribers in Q1 roughly 500 physicians treat 50 percent of HAE patients and our team has reached nearly all of them. Most of these physicians tell us they intend to prescribe Orladeyo, but only a minority have done so far. So there is a lot of room for growth. And finally, payers are reacting favorably to Orladeyo, most of the reimbursed products in q1 came through medical exemptions, but many payers and pbms also established coverage policies our momentum with payers is strong And we expect the great majority of patients to have access for Orladeyo by mid year.
The most important investment we made in this launch was building an experienced commercial team that knows how to execute. our US General Manager Alan Hach and our US VP of sales on Ron Delenger launched Cinryze over a decade ago and successfully created a first market for HAE prophy. They came to buy for us because they always knew that an oral drug is what HAE patients really wanted. They attracted a talented and agile team that understands the importance of fighting for every patient in a competitive Rare Disease market like HAE.
As excited as we are about the Q1 results this team is just getting started. COVID is limited in person sales calls. But vaccines are starting to change this. Our marketing programs are just starting to kick in. And expanding reimbursement access is giving patients and prescribers even more comfort in switching to Orladeyo.
We are very confident about the growth trajectory, and we believe Orladeyo will reach peak global sales north of $500 million. The US is the first and largest part of that opportunity. But we expect meaningful sales in Europe. awareness and understanding of HAE in Europe is on par with US but use it a targeted HAE prophylaxis has lagged based on lack of options, our work with European physicians and patients tells us that the availability of new options and specifically an oral once daily therapy well more than double prophylactic treatments share to 60% or more patients. We are taking the same approach in Europe as in the US. Investing in experienced commercial teams that know how to law for these products. Orladeyo will launch in Germany this quarter, and early access programs are active in France and the United Kingdom. We look forward to sharing more about Europe in the coming quarters. And there is yet another Orladeyo launch underway right now in Japan. I’ll turn the call over to Megan to describe how our partners at Torii pharmaceutical are approaching this opportunity.
Megan: Thanks Charlie. We’re excited the Japanese launch is now underway after successfully completing the NHI price negotiations last month. There are a few important points I want to emphasize again regarding the commercial opportunity in Japan, and what makes it different from the US and Europe. First Orladeyo is the only approved prophylactic therapy in Japan. There’s no competition, Torii has a head start in building the prophy market. And our oral once daily medicine is well suited for our population that tends to prefer oral drugs over injections. Secondly, while the vast majority of HAE patients in the US and EU are already diagnosed, Japan lags behind. Only about 20% of patients are identified in registries today. Torii is focused on finding patients and helping to advance their standard of care by providing access to the first approved prophylactic medicine.
One reason we chose Torii was based on what they accomplishment with Gilead’s HIV franchise, their strategy focused on driving disease awareness among physicians and increasing patient identification. This strategy was very successful as they grew the business to almost $200 million annually.
This experience serves as a strong foundation heading into Orladeyo launch. And similar to us, Torii’s been preparing well in advance to our fully focused on supporting a successful launch. Lastly, through our partnership economics, we have triggered the $15 million milestone payments following pricing. And we get to share in 40 success within a tiered royalty from 20% to 40% of net sales.
Overall, the Japanese market provides an outstanding long term opportunity, we see a strong potential to follow a path similar to what we’ve seen in the US in the last decade, an expansion of the HAE market driven by patient diagnosis and adoption of prophy treatment as part of standard of care.
As Charlie shared, there’s a lot of early momentum in the US launch and we’re not surprised by this excellent start. Over the course of this year, you will continue to see new clinical data highlighting how well patients do on Orladeyo over time, patients are getting their disease under control while reducing the impact treatment has on their lives and independence.
Our work is also helping physicians understand how it works today with an ideal treatment choice for all patients. It offers patients the attack control they desire and the lifestyle freedom and benefits of a convenient were discreet oral once daily pill.
Our strategy remained focused on shifting this treatment paradigm. As Charlie spoke about earlier, patients are switching which is early evidence our strategy is working.
We see a very similar unmet need and opportunity in the complement space with our factor D program. I’ll now turn it over to Bill For more on our 9930 progress bills.
Bill (CMO): Thanks Megan. for everyone who discovered and developed Orladeyo and clinical trial collaborators around the world, It’s just so great to see Orladeyo launch going well. For hereditary angioedema, Orladeyo is effective and safe and because these are all dramatically reduced therapy. A very simple shift is beginning for patients with PNH. A very serious diseases, we have no approved oral treatments, and the standard of care is life long intravenously of these infusions is 9930 has a great opportunity to substantially improve disease control in the PNH, compared to the currently available intreavniously infused C5 inhibitors. These do a good job controlling intravascular humolouses that many patients remained anemic, are still transfusion dependent and continue to suffer from symptoms like fatigue. That’s because C5 cannot control extravascular hemolysis, the clinical advantages Come on top of the obvious patient benefits of our administration. And we are moving the program very quickly to get these medicines to patients with a PNH. I’m pleased to report that we have reached agreement with the FDA on both the design and the end points for our PNH pivotal trials. The two pivotal trials, each test, oral BCX9930 monotherapy. And will support the indication PNH. The dose will be 500 milligrams the BID.
One trial will include patients who had an inadequate response to C5 inhibitors and the other trial will include patients not currently receiving compliment inhibitors including those Nieves of these drugs.
Patients in both categories need relief of anemia freedom from transfusions release of symptoms. The primary endpoint for the both pivotal trials agreed with the FDA will be change from baseline hemoglobin a direct clinical measures of relief of anemia. In both trials, we will measure the impact on need for transfusions as a secondary endpoint. And we will also capture other important outcomes in PNH, such as fatigue scores, PNH, clone size, and laboratory biomarkers of hemolysis. The outstanding results we reported in March, we maintain unchanged from baseline 3.3 grams per deciliter and C5 inadequate response patients and 3.5 grams per deciliter in treatment nieve patients position BCX9930 very well for success in our pivotal trials.
As you heard In March hematologists and patients with a PNH are very excited about the prospect of a treatment that could have dramatically improve outcomes and eliminate the need for IV infusions. We are convinced that success in our pivotal studies will drive a paradigm shift in PNH towards oral proximal complement we envision in BCX9930.
So what’s next in this program, we are now ready to move directly into the clinical trials in PNH in the 2nd half of the year using the designs now agreed FDA we’re also moving into a proof of concept trial in selected nefriatious indication in the 2nd half of this year. BCX9930 represents a pipeline in a molecule and we’re very excited to be moving this program so quickly because we know patients are waiting. Now I’d like to hand call out to Anthony.
Anthony: we’ve continually said that we are focusing our investments where they can drive the greatest value. With a Orladeyo now approved in three key global territories. The commercial team, the US getting along to offer great stars and a very positive data that we have of BCX9930, we are executing this strategy. And we are well positioned for future growth. You can find our detailed financials in today’s earnings press release, I like to call your attention to a few items. net revenue for the quarter was $19.1 million. Of this $10.9 million came from sales of Orladeyo in the US. Our operating expenses not including non cash compensation for the quarter was 63 million. With the incremental investment from previous quarters focused on the development of the BCX9930 we ended Q1 with $244 million in cash. This cash in addition to access the additional 75 million from Ethryium, and now revenue from Orladeyo continues to give us cash runway into 2023.
Since this is our first full quarter of Orladeyo revenue, I want us to take a minute to remind you of our approach and key items. We recognize revenue when our soul source specialty pharmacy ships Orladeyo to patients for use. Each shipment contains 28 days supply of Orladeyo. these are shipments directly from the specialty pharmacy to patients. So they approve sales and you will not see any inventory or channel stocking and our revenue numbers. When we look at gross to net, the biggest impact at the moment will be non reimbursed shipments, our quickstart program has proven to be a real differentiator. And it is delighting customers and the ease and speed of getting access to Orladeyo sometimes within 24 hours of the star form being submitted. The Quasar program and our patient Assistance Program both resulted in gross to net being higher now than it will be once the launch is in a more mature phase.
Because gross to net is so fluid early in the launch. We are not providing gross to net and guidance. But as we continue to progress with the launch, you should expect our gross to net adjustments to move in line with other rare disease products. So what our strong Q1 mean for future periods, Charlie team did a great job of converting clinical trial patients giving us a boldness of patients in the first quarter. Additionally, the team has achieved great success and helping many new patients suite from injectable, prophylactic or acute only medications. together this gives us a really strong foundation for future periods. We have not provided revenue guidance as there are still several variables that will impact the growth trajectory and revenue that we need more time to better understand first, what is the steady state of monthly prescriptions. While we’ve been very encouraged with numbers today, we need more times to see it play out. Next what does customer retention look like over a longer time. In our clinical trials. This number was about 75% through 48 weeks telling us that Orladeyo it was well tolerated and is providing outstanding attack control. While we believe we will see there’s a level of persistence in the market. It’s still too early to confirm that this is the case. And lastly, what do the trends look like when the vast majority of patients have reimbursement, the $10.9 million in net revenue we are reporting is only from patients whose prescriptions are reimbursed. As currently described, we’re making good progress getting Orladeyo onto policies. But the pace of reimbursement over, especially the second quarter will be a key driver and the rate of revenue growth for us over the remainder of the year.
While we’re early in the launch, we are very encouraged by the results today, we have a lot of work to do a lot more patients to get this next generation of drug to we’ve got a great product in Orladeyo there are strong patient demand for it and we have the team to execute on making our launch a success and getting us to our key target of $500 million plus in the years
John Stonehouse (CEO): thanks, Anthony.
This is what execution looks like. We’re off to a great start with the launch of Orladeyo in the US and starting to launch and other major parts of the world, all contributing to what we believe will be a $500 million plus global peak sales product. Add to that our plan to advance pivotal studies in PNH with 9930. And parallel moving into other indications with this pipeline in one molecule. And finally, having a financial flexibility that comes with a strong balance sheet, and revenue generation allows us to focus on execution and value creation. The evidence is clear that BioCryst is transforming into a company with product revenue, a full pipeline, and a discovery engine that produce these compounds, and will continue to produce more.
That concludes our prepared remarks. We’ll now open it up for your questions.
Jessica (JP Morgan): Hey, guys, good morning. Congratulations on a strong quarter. I was curious if you could add some more color about specifically which agents you see the patient’s switching on to Orladeyo or switching from?
Charlie: Hey, good morning, Jeff. Thanks. Thanks for the question. We’re seeing patients switch from all the different therapies really in proportion to what you’d expect from the market or market share. So as I mentioned, more than more than half the patients are switching from an injectable prophy, and that is takhzyro, haygarda, cinrise. proportion to their market share.
Jessica (JP Morgan): Okay, thanks. And you mentioned that some scripts were not reimbursed in a quarter, can you say what proportion of first order shirts are not reimbursed?
Charlier: Yeah, we haven’t. We haven’t commented on the specific details. But as Anthony mentioned in his comments, what we’re what we’re doing with nearly all patients is starting off in our quickstart program. And then we work with patients and providers to go through prior authorization. And in Q1, most patients got access through medical exemption. But we’re making great progress with payers and we expect may continue to progress through mid year.
John Stonehouse (CEO): And Charlie made comments in his prepared remarks around the more policies that are in place where all the data is on formulary, the more interest there is going to be by both doctors and physicians.
Jessica (JP Morgan): Got it and the last one on growth and as you mentioned that longer term in line with other rare disease drugs, too. Can you just characterize what typical gross to nets are in rare disease?
Charlie: From a from a growth perspective, what we’d be looking at adding is kind of into the teens 20 type type of frame.
Liisa (Evercore ISI): And I wanted to add my congratulations on a great quarter. I’m going to turn to the PNH study for a moment. Can you discuss what sort of control will look like and over the site
Bill (CMO): Thanks for the question. Super excited about today studies of course, and one study will be a superiority trial against C5 inhibitors in patients who’ve had the inadequate response and the other study in patients who are not taking C5 inhibitor, it will be controlled or it will be placebo.
Liisa (Evercore ISI): Okay. And can you maybe describe the, I guess, how You’ll be looking at some period of C5, will you be looking at combination therapy then for for the patients that are inadequate responders or will people be monotherapy? How will that work for the inadequate group?
Bill (CMO): Sure. Both studies are designed as monotherapy. So our patient will be randomized to in a C5 inhibitor trial, be randomized to continue their current treatment, or start BCX9930 monotherapy and discontinue their current treatment. So this is the goal here is a label for monotherapy. broad indication to treat patients with a PNH. But the reason for the study designs as we’ve just outlined, this is to support that topic lately.
Liisa (Evercore ISI): Okay, and how do patients go onto monotherapy from from being on a C5? How does that work? is it just a cold turkey switch or is there a combination therapy and then a withdrawal?
Bill (CMO): The C5 inhibitor is stopped and then 9930 is started. It’s just simple switch.
Liisa (Evercore ISI): Okay. We haven’t seen that data yet in that population in terms of being on monotherapy. can you give sense of what is was like to see that in your phase one, phase two?
Bill (CMO): The protocol doesn’t specify the particular timeline and the physician judgment call, but we plan to share data by the end of the year, right now neither the regulators nor us are waiting for that data to start studies. Because we’re very confident in the drug on the basis of the monotherapy results from the nieve patient population, the diseases is that disease, factor D is the same. So it’s not necessary for us to see that before we start those trials.
Liisa (Evercore ISI): Okay, good. And then I guess just turning Orladeyo, really great out of the gates, is there any kind of additional color you can provide on either you know, the percentage of patients that were on your quickstart program, receiving or that way, you know, the percentage of prescriptions, like anycolor on persistent, those are obviously the key questions to help guide us as we think about, you know, the rest of the year, launching off of this really a great start. So, tell me, who provides additional color there? And as a final question,
Charlie: Surely it is so so on a percentage of the Quickstart. So, in Q1, nearly all patients started on on quickstart. net, that’s part of our strategy, as we work with them to get access. And as I mentioned, your most patients got X or got reimbursed through medical exemption. If they were not able, we were not able to do that. And he wanted to continue on pretty good until the payers established policies. And as as as far as your question about persistence, as Anthony mentioned, we said we had great results in our in our clinical files that about 75% of patients staying on for at least a year. That’s what we expected in the real world. So far, the patient experiences being great, but it’s too early to say well, the long term persistence rate will be
Liisa (Evercore ISI): okay, and I patient quickstart program is about is it a monthly prescription?
Charlie: That’s right. It’s a month in it. And if there’s not reimbursement in a month there, we will continue on either on quickstart or on our patient Assistance Program.
Liisa (Evercore ISI): Okay, I got one final question. And approximately how long are they taking the day off from our Quickstart plan.
Charlie: So again, q1 is all over the board everything from a few days to patients still being on the program, and by mid year we expect that to really stabilize as early patients will have access to coverage through their plans.
John Stonehouse (CEO): Yeah, and Lisa the theme here is that as the year progresses, we will have more and more people paid drug and fewer and fewer Quickstart that’s that’s the plan.
Kashitori (Cowen & CO): Hey guys, congratulations. On the early progress. Just wondering we hear really good things about the interactions on both a clinician and patient level via your hub. So just wondering, as it seems to be ramping a little bit faster. Do you feel your staff would appropriately Can you talk about some of the early learnings from this really kind of more personalized approach and things that getting underway that you’re maybe changing? Or again, if you’re staffing a little bit more then on EU, just wondering looks like a potential really focus selling effort to talk about where these patients are domiciled, is it gonna be fairly easy to get at them? fairly difficult? Maybe some of the learnings from getting back to the old I know you feel, and we feel as well that things should go better there, but maybe a little bit more nuance around Europe. And then lastly at for Bill, I know, it’s really early, just announcing you’re going to start these pivotals. But if you take a shot at timing of results, maybe a little bit of nuance here in terms of the kind of competitive landscape to enroll patients, but any kind of shot at when we might expect to see data would be fantastic.
Charlie: thanks for the questions can. So the first question you had was about our specialty pharmacy patient services program and staffing. One of the great things about having us all sources we really prepare for the right staffing, Alan Haj and his team have done a great job working with the SP that hit it as easy as that and from patients. So increasing staffing and appropriately increasing procedures. They’re really quick and making those those changes. So to serve the patients well, and is making a difference. As far as the EU really good question about you know, access to patients. And how easy or difficult is that? The great thing about the EU is that treatment centers are very concentrated. So you can literally have hundreds of patients within a given center. And so what our teams are doing is working with the HAE experts in those centers, to make them aware of that Orladeyo coming and to reach out to their patients and bring them into the center. So we’re really enthusiastic about the opportunity there.
John Stonehouse (CEO): And I add that, you know, biocrsyt is a known entity to these docks that HAE and we’ve been into clinical trials all the way back to our first generation program. And so we’ve got fantastic relationships, and they know the company, they’ve been involved in our trials. And so they’re the excitement level high.
Bill (CMO): So again, one of the great questions, when we will studies finish, I wish I could give a specific answer, I think it’s really difficult because we need to get them up and running, what I can tell you is that we have a great clinical execution saying here at BioCryst. And we are going to approach this on the basis of the patient’s for me, this drug is going to be a major advance in PNH is what we believe and so we’ll be ready as fast as possible. And just like HAE, we will go to the best centers all around the world. And just like HAE, in most diseases, getting patients on clinical trials is a competitive activity. And we believe we have a great offering here with all faculty. We look forward to seeing the study start on critical reading, they will they will be in a better position to finish.
John Stonehouse (CEO): just add, it’s hard to say because we just don’t know what their rate of enrollment will be right in a competitive space and, you know, much larger study than what we studied so far in PNG. It’s just super hard to predict. But one thing I will say is, Bill’s team is excellent. And their aim is to be the sponsor of choice. And this is where being big doesn’t necessarily help, us small companies that pay attention that listen that give the extra TLC make a difference in enrollment. And so I am super confident that those those people do that.
Serg (Needham): First of all, you may have disclosed this before, can you disclose the number of patients that were on drugs at the end of the first quarter and I guess how many of them are patients transitioning from clinical trials or the Early Access Programs?
Charlie: We have not disclosed that detail on that. And what I can say is the number of patients on Orladeyo will continue Instead of bro everyday agents switched on now, in q1, what we did say is that the majority of patients, by the end of the quarter were those were new patients switching to Orladeyo, and then the rest of them were those transitioning from our clinical trials and EAP. And that transition program finished in q1, so that that boldness that Anthony talked about is, is complete, and everything going forward is his role as patients switch.
John Stonehouse (CEO): Yeah, just one point of clarification on that complete means that there’s different clinical trials to Quickstart or our patient assistance, they have to go through the same process of reimbursement like any other patient and so some have been reimbursed some have not.
Serg (Needham): Okay. And he talked about position pays about 500 serving about 50% of the he patients How big is his next set of physician serving the other 50% that you need to address?
Charlie: easily another 1000 plus physicians out there and we’re we’re reaching that as well, we’re really concentrated on that, that top 500 just because they are you know, they have more patience, and they really know HAE so that’s our priority, but we’re reaching out to doctors as well. And we’re getting getting prescribing from from them too
John Stonehouse (CEO): what makes this achievement in the first quarter with Charlie and his team even more remarkable, they did it in COVID. Right? And so we’re already seeing things starting to open up with activation, that’s only gonna get better as the year goes on.
Serg (Needham): Okay. All around COVID. You know, what, what has been the overall impact with restrictions? Are you seeing the limitations on the number of patients switches? And is that something that you expect will increase as the sessions left?
Charlie: I think first first of all serg we talked about how COVID limited our in person interaction with providers, fewer than 50% of our calls were in person that’s going to make a big difference is we’re able to do more in person visits. And it we had a great quarter despite all of this. Another piece is that the oral is is easy for doctors to prescribe. So it’s something that many physicians have been comfortable prescribing Oraldeyo in a remote environment to their patients with more in person visit so it’s just it is more opportunity and we’re excited for what’s to come.
Raycroft (Jefferies): Hi, this is Kenny Shan on behalf of Raycroft. I have two questions, one on Orladeyo. How’s the progress on the formulary adoption versus reimbursement by medical exception? have you encountered any pushback on the cost effectiveness from insurances? And how are the reimbursement conversations going? Are insurances looking at ISO reports? And for the second question on the PNH program, was the FDA feedback on ldh levels? And is there a specified ldh threshold that would trigger a safety concern? Thanks.
Charlie: Yes, thanks, Kenny. As far as the payer progress and policy progress is, as we said on our conference going really well. In q1, it was mainly medical exception that we were getting access but several payers and pbms put Orladeyo on formulary. And we accept we expect a lot of acceleration that over the over q2 cost effective is no this is the lowest price prophy on the market. It appears that it reacted really well for pricing strategy, as well as the profile of the drug. And as they see the demand coming from patients switching to Orladeyo is really encouraging payers to establish coverage policies quickly. So we’re very pleased with where we are.
John Stonehouse (CEO): And let me stress one point I made in the prepared remarks. This drug works, right it people are switching that are controlled on prompt therapy to our drug either staying on our drugs. So this idea of effectiveness this drug work is really want to stress
Bill (CMO): Okay, thanks for the question. We do have a secondary endpoint of percentage change from baseline ldh. There is no threshold either as a endpoint or the safety concerns for that matter. LDH is a useful biomarker, the improvement in an anemia with a change in the baseline in hemoglobin, hemoglobin going up, and the improvement in transfusion burnden with transfusion avoidance staying course the most important number transfusion going down. They’re the Important clinical outcomes.
It’s also worth stressing. And another very important secondary endpoint is quality of life tools such as fatigue score. so important measuring fatigue is important too.
John Stonehouse (CEO): And Bill, you might want to talk about the interaction with the FDA, and how it was focused on clinical benefit. biomarkers are important, but clinical benefit is more important. Right?
Bill (CMO): So really glad to see clinical outcomes being treated as important endpoints in clinical trials. So that’s why we have change in baseline in hemoglobin the primary endpoint and transfusion avoidance as the secondary endpoint and evaluating treatment of anemia, after all, so there’s a whole range of interesting biomarkers to measure. ldh is not viewed as important and after the primary endpoint is really very simple.
Brian Abraham’s (RBC): Hey, good morning. Thanks for taking my questions. And congrats as well, on your launch. My first question is, is on a launch. I was wondering if you could maybe parse out the pent up demand for patients new to orladeyo. I’m wondering how long into the year might you expect first quarters rate of switching from existing acuter prophylactic therapy to continue?
Charlie: Good question. And yeah, there was pent up demand. And we expected that. So they’re they’re always early adopters, what we’re really pleased about is the demand is continuing. So we’re seeing patients switch to Orladeyo, literally ever every day. So as I mentioned in my remarks, there’s a lot of opportunity to come as all these physicians, who we’ve reached that hadn’t yet prescribed, that are telling us that they’re planning to have a conversation with their patients and prescribe in the future. So a lot of opportunity to come throughout the year.
John Stonehouse (CEO): Yeah, we don’t think this is just a, you know, one quarter pop. And then Peter out, we expect that this is going to continue to be strong through the course of the year. And we said it’s a $500 million plus global peak sales product. And we’re even more confident in that.
Brian Abraham’s (RBC): That’s really helpful. And then I’m curious what sort of feedback you’re getting on how real world efficacy and safety and tolerability is comparing for the clinical trial setting. any surprises there? And then I know it’s early days, and I’m curious what you’re seeing with respect to the persistence and compliance for the new patients to the therapy versus the rollovers from the expanded access
John Stonehouse (CEO): I’ll take that first Charlie. So I’m smiling, as you asked that question, because the docs, and patients told us that these drugs do way better in a real world than they do in clinical trials. And so I think our clinical trial doesn’t really represent the real benefit that we’re seeing from patients Megan mentioned that, you know, we’re looking at the data from Apex to, you know, out to now now he six weeks and it just keeps looking better, right. And so, this, you know, I’ll say it again, this drug works, people are getting a real benefit. They’re getting control of their disease. And oh, by the way, they’re doing it on one capsule once a day. So it’s just a huge, huge benefit.
Charlie: And Brian, as your question about the experience of rollovers versus versus new patients. The great majority of the patients who are in our clinical files, chose to continue on Orladeyo in the commercial world. And because they’re having such a great experience and the early word from patients that we hear back from our specialty pharmacy, and we hear back through physicians, via our reps, the early feedback is very strong. Patients newly switching to Orladeyo or having great experiences as we expected so we’re pleased and to my point earlier, we expect more patients to contain to switch to Orladeyo out based on what they hear from their peers about their experience.
BOFA: as it relates to treatment nieve patients. What is your latest market data telling you about the percentage of patients to having HAE who are currently not on any therapy? And related to that? I’m just wondering, do you think, you know, when COVID you know, starts to clear and more offices start to reopen that the percentage weight of new patients or treatment, ie patients that are receiving scripts will normalize more relative to what you were seeing in the early stages of the launch, and then have a couple of follow ups.
Charlie: I think I got your question. Let me let me address it in a couple of different parts. What we saw prior to the launch of Orladeyo, about 60% of the patients are on prophylaxis. And so in the first quarter, we’re seeing more than half of the patients coming to Orladeyo of switching from those other prophy products, most of the remainder of patients switching to Orladeyo or switching from the only treatment. So they may be naive to prophylaxis, but they didn’t treat it with acute only. Our research tells us that the number of truly HAE treatment naive patients, you know, they’re not on acute not on prophy is small. That’s a small opportunity in the future. But but most of these patients are treated well by their doctors, they had at least an acute therapy. And those patients are deciding to switch Orladeyo. Now that they can do it with an oral once daily option.
John Stonehouse (CEO): So this is a I can’t stress this enough. This is a switch strategy. And it’s working. Right that is if you walk away with anything today walk away with this is a marketplace where people are on prophy therapy and acute on demand therapy and are switching to a world drug. Right. So that’s what we we saw that in the market research. We saw it in clinical trials, and now it’s playing out in the marketplace, which is great. And it’s only the first quarter to enter your point about COVID. I think there’s an opportunity here, right? I think, you know, access of our reps to Doc’s has been challenging in some parts of the country. Yeah, they’ve been really diligent and resourceful. And they produce great results in the first quarter. But I think as things open up more, it’s gonna get better. I think the same goes for doctors and patients. Right, you know, it’s just that harder to telemedicine. Maybe they’re putting off their visit. And so I think that gets better as more people get vaccinated, and more people start to go see their doctor.
BOFA: Okay, thanks for color Jon. in terms of, Japan. I know it’s just very, very early in the launch, but in terms of their trajectory would you expect it to be similar to what we wouldn’t expect to see in the US. And do you have any visibility on our pricing in Japan,
Megan: Sure, sure. So on the trajectory to being I think, as we were sharing Japan is a very different market than the US and Europe and a decade behind. And so we’re absolutely thrilled about the opportunity that Torii has to really build and shape it. So I think our trajectory in the in the near term is more tempered, also to Japan is in a state of emergency currently with COVID and different rollout with vaccines. And that may also slow that initial ramp but as I shared in my remarks we see this as a really strong long term potential as Torii drive the adoption of probate, but also the expansion of the market through through more diagnosis and treatment. And then to your to your second question. With our pricing, negotiations completing last week, last month, excuse me, we netted out with a price or around 250,000 US dollars per patient per year. And we’re obviously we’re really proud and excited about that price point and, and the opportunity it represents for patients and for Torii. So all in all, they’re they’re equally excited to now be out of the gates like the US have been for the last few months, and we’re excited to see what they can deliver.
BOFA: Okay, thank you. And then at just one question, if I could on on PNH for a few trials that you’re running. I know it’s a difficult to take a guess on how long it’s going to take to enroll but naive versus the placebo, the inadequate responder trial excuse me, would you expect both to read out and around the same time? One could enroll faster than the other?
Bill (CMO): Yeah, sure. It’s very difficult to say either of those possibilities could have come to pass or they could agree that approximately the same time or one could move forward much more quickly than the other, its too early to know.
Wong (Barclays:) Hey, good morning. So just one question on PNH, can you tell us what the size of the trials could be, or this phase three, and then like what specific tkp data was looked at to go ahead with the 500 meg, big dosing versus versus 400.
Bill (CMO): Thank you questions. So we’re going to reserve additional details about the studies for later this year. Maybe at a medical meeting or something like that. We’ll be happy to share all those details have their stage names, submission, those the PK PD modeling, uses all the information you have, for example, on in vitro on cosmote assays and things like clinical outcomes and biomarkers ldh. This is early ldh actually quite useful as a as a fairly rapidly response to a biomarker that follows the dosing. And before that disclosures through last year, about how the high doses are obviously, superior to load those into motion that goes into the ball rolls. And of course
John Stonehouse (CEO): let me just add on the size. I mean, these are very rare disease trials, right. And so, you know, typically in rare disease trials, you need a couple of 100 patients on the drug for a year for safety as a cryotherapy. And, you know, the expectation is, it’ll be something like that. I think we ended up bill with over 300 in the HAE program when we filed so.
Wong (Barclays:) Okay, thank you. And then one follow up question. So for the slightly higher level that we see or ldh levels previously, maybe was due to shorter duration of treatment and a small sample size. So do you expect 500, maybe a little more time to get you below that 1.5 offer limit?
Bill (CMO): So the particular target is not an endpoint. So that’s the most important response to the question. In fact, so are there is nothing magical about 1.5 times Apple lbh. And certainly, certainly useful binaca. And we measure it, and is included as a secondary importance more relevant in the setting, when you say high ldh therapy, that’s not as important as increasing or reducing the transfusion but improving. So specifically, the question I think, what you’re saying in all the other studies of all of the combo inhibitors, when sponsors have published individual patient data over a long period of time, you see the ldh fluctuates and there will be so much to fluctuate over time, but people are not being as transfused and feeling well. They need to achieve all the principal objectives of treatment.
John Stonehouse (CEO): Yeah, what’s most exciting is we now have agreement with the FDA that hemoglobin is the primary endpoint change from baseline which is really exciting.
Jonathan (JMP): good morning and sharing my congrats on strong launch. Just a few for me. I’m wondering if the 10.9 million figure for the Orladeyo, if that’s net of your royalty payment and if there’s any meaningful contribution from ACU in France. Yeah, so that a $10.9 million is not a match of the royalty payments. The royalty payments are just as a reminder, 8.75% of those net revenues up to 350. And then once we get over 350, it drops down to 2.75. where it hits is, you know below the line between operating income and net income Basically as our interest expands, in terms of the AG.
John Stonehouse (CEO): That was all US sales at that point I.
Jonathan (JMP): Great. And then just one question on the market where you’re seeing patients switch from acute, you had any sense on the percentage of patients now of all patients were on prophylaxis. And where do you think that kind of leveled out and I’ve used it and now when you have on the market, and you’re seeing more switched over the prophylaxis in
Charlie: question, john, so imagine what we see, we’re very confident that at the time that he wrote a lot about 60% of us HAE patients were on prophylaxis. And so the patients also switched from acute therapy only to Orladeyo, that number is going to grow. And what the physicians tell us is that in the future, they expect about 80% of patients to be treated with prophy so the acute market is shrinking every day. And we expect that same kind of trend to occur in Europe after our launch there.
John Stonehouse (CEO): It turns out that the market research that Charlie has been doing is playing up the marketplace.
Jonathan (JMP): Well, thanks for taking the questions and congrats again. Thanks. Yeah. Thanks, john.
John Stonehouse (CEO): So I’ve done a lot of earnings calls in my 14 years at biocryst. And I gotta say, this is one of the the most fun and exciting ones that I’ve been a part of, you know, we’ve got a great launch with a great product and a great team. And we’re just getting started. And so I was really excited to have a product that’s generating real revenue. We have a green light to go into pivotal studies with our next program. That’s an entire pipeline in a molecule. And so we’re going to be starting up pivotal studies later this year. So it’s going to get a whole lot better than that. And you know, our focus now with execution. I’m just so proud of the team, and just incredible focus and execution that that they delivered and will continue to deliver on so thanks for your interest in our company and have a great day. Ladies and gentlemen, this concludes today’s conference call. Thank you for joining to notice and have a great day