We offer an equity analysis subscription service. Try us out with a free trial, cancel anytime and begin saving your valuable time and gaining access to the research you need! View our offerings here.
Brian Abrahams (RBC Analyst): Senior Policy Analyst here at RBC capital markets. And thanks for for joining us for this afternoon sessions at our healthcare conference. Our next featured company is biocryst pharmaceuticals. And we’re really glad to have many members of the senior management team here with us. In what’s been a very exciting and eventful time for the company, john Stonehouse, their CEO, Anthony Doyle, their CFO, Charlie Guyer, their chief Commercial Officer, they’ll share it in their chief medical officer, Megan sinskey, their Chief Business Officer, Helen factory, the Chief r&d officer, and john bluth, head of investor relations. So team, thank you guys so much for joining us. Really appreciate it.
Jon Stonehouse: Thanks for having us, Brian.
Brian Abrahams: Great, well, maybe just kicking off on the most recent commercial progress with Orladeyo, you’ve had a strong launch of the drug out of the gate in the first full quarter? Can you talk about some of the trends that you’re seeing on the ground? And what gives you comfort that the strong trajectory is going to be sustainable?
Jon Stonehouse (CEO): Yeah, let me start Charlie, and then a pass it to you. We’re going to be making some forward looking statements all of us are and I just point you to our website for the risk factors associated with those. So to answer your question, specifically, we’re just getting started, Brian, and, you know, it’s COVID access, you know, has had its challenges, although our team has done a spectacular job of getting to physicians, but and most of the reimbursement thus far has been medical exception. So, you know, we expect that that this trend will continue. And we’ll fill the funnel even further. With each week we’re getting, you know, more and more patients on on drug. And with each week, you know, we’re getting more people reimbursed. And so all the signals are that, you know, this is definitely sustainable. But Charlie, you may want to add a little bit more color. Sure,
Charlie Gayer (CCO): yeah. Hey, Brian. So I think there are two trends to add to what john said, that give us great confidence. Number one is that patients are switching. So this is what we expected from our market research or clinical trials, but it’s happening in the marketplace. So patients first starting Orladeyo, in the first quarter, more than half of them are switching from injectable prophy. The others are coming from acute only. So we’re really pleased about that. And then the other thing is our prescriber base is expanding very consistently, and even amongst top HAE treaters who have not yet had the opportunity to prescribe which, frankly, at this point is the majority, the intent to prescribe in the future is really high. And so in addition to what john said about improving market access, all of this bodes both nicely for the future.
Brian Abrahams (RBC Analyst): That’s great. And then maybe expanding on your comments with respect to access and reimbursement, how quickly would you expect for the day to move beyond medical exceptions to get onto formularies? With established coverage policies? What’s the process like there?
Charlie Gayer (CCO): It’s going well, payers are responding very favorably to Orladeyo. And the demand that they see from patients. By mid year, we expect the majority of the great majority of patients have access for Orladeyo coverage through their PBM or or payer policy. So we’re we’re pleased with how that’s going. And we think once we have even broader access, that’s going to give more customers the confidence to prescribe and try Orladeyo.
Jon Stonehouse (CEO): Brian, I’d add that this is part of our strategy, right, it’s filling the funnel with as many patients as we can. And that then drives the medical exception, which is a burden on the payer and draws them to the table. So, you know, I think it makes this result of the 10 point 9 million in net revenue even more remarkable given that the majority of it was medical exception.
Brian Abrahams (RBC Analyst): Got it. And how should we expect gross to net trends to evolve over the course of the year, especially as reimbursement access becomes smoother.
Anthony Doyle (CFO): Yeah. So you know a lot of our focus, Brian has been getting drug to patients who wanted and so right now, a lot of free product through our quickstart product is going out. So at the moment, it’s higher than it will ever be. what we’ll see is over the course of time as the launch matures and later in the year, second half of the year will normalize around you know 15 to 20%. So in line with other rare disease products.
Brian Abrahams (RBC Analyst): Got it. And you talked a little bit about this. The switching patients can can you expand more on the types of patients you’re seeing start on or the Orladeyo, since the launch and maybe how this has changed, as the months have gone on? I’m curious about their levels of disease severity, the types of drugs that they’re they’re switching off of? What are some of the trends you’ve seen? And have there been any surprises?
Jon Stonehouse (CEO): Charlie, let me start. And then then I’ll pass it to you for more specifics. But we’re not surprised by it. I think maybe some people on Wall Street are, but we certainly weren’t. We said this was a switching market from the get go. And that’s exactly what we’re seeing in the real world is that patients said, are satisfied with their injectable therapy, want to lower burden of their therapy by taking a once a day oral. So we’re really excited to see what we saw in our market research and in the clinical trials play out in the marketplace. Charlie, you want to add anything?
Charlie Gayer (CCO): Yeah, sure, Brian, as I said, more than half the patients in q1, we’re switching from those injectable prophy products. And so that’s that’s all of them. And it really in proportion to what you would expect from their market share. So takhzyro is the most common switcher than heegaard and cynrise, pretty much in in that order. And then they’re more patients switching from acute only now that they can go to a prophy with just one pill once a day, that that’s helping us expand the prophylaxis market.
Jon Stonehouse (CEO): The other thing I’d say, Brian, is they don’t look at the market is, you know, mild, moderate, severe. You know, if you’re having an attack, you’re having an attack, right and doesn’t matter. You know, what location it you know, it’s a problem. And so this idea of having one capsule once a day to prevent attacks is huge. And that’s why we’re getting a switching from injectable prophy. And we’re expanding the prophy business and getting acute patients to switch as well.
Brian Abrahams (RBC Analyst): Got it. What are your expectations for long term persistence on the drug based on what you’re observing? Now? I know it’s it’s it’s somewhat early days to gauge that. But are there any metrics that you’re using short of longer term longitudinal data, things like refill rates and our x tr x ratios to gauge what compliance and persistence look like, at least in the in this early phase of the launch?
Jon Stonehouse (CEO): Yeah, I’ll start with, you know, what we expect. And, Charlie, you may want to get into the specifics specifics of you know, the fact that we got a sole source specialty pharmacy, the info we have, and also the work we do to set expectations and monitor patients on therapy. But Brian, in our clinical trials, we saw 75% of patients in Apex to stay on through 48 weeks. And so our expectation is that a lot of people do really well on our drug. And and so far in the marketplace, we’ve seen a similar retention rate. So so far, so good, Charlie.
Charlie Gayer (CCO): Yeah. And john, what what is your talk about setting the expectations? Some patients do, it’s not most patients, but some patients do experience, gi side effects, they tend to be mild, they tend to go away early in treatment. And so we set those expectations, our sales team sets that expectation with the doctors. So that that’s passed on to patients at the point of prescription, and then our specialty pharmacy team, the care coordinators, and the pharmacist there set those expectations with patients that this is normal at attempts to go away. And we think that that’s, that’s really helping drive long term persistence. And then we do we get terrific data from our sole source specialty pharmacy, so it’s something that we watch closely. The early returns on this are positive, both in terms of persistence and compliance.
Brian Abrahams (RBC Analyst): Got it? And you talked about the real world safety experience a little bit. What’s the real world efficacy experience like? You know, anecdotally, I know, you know, now you’re sort of at a point where many of the patients on agents like takhyzro will have sort of be washed out, fully washed out of any effects of their, their, the previous drug that they were on, so it’s really a good, you know, litmus test for how well, patients will probably do over the long run on Orladeyo, I guess what are you seeing? What are you hearing? anecdotally, I know, you know, real world experience can sometimes be different from from clinical trials. And are there any I’m also curious if there’s any types of patients who you’re hearing are responding better in the real world than others?
Jon Stonehouse (CEO): Yeah, we were told by patients and physicians who treat HAE that these drugs typically do way better in the real world than they do in clinical trials that clinical trials aren’t a good reflection of the benefit of the drug. And so, you know, one of the things we saw in the clinical trials was this really high retention rate, people aren’t going to stay on the drug, if it’s not working for them, right. And so we’re seeing the same thing in the marketplace that you know, people are going on staying on. And so And remember, stress is a trigger in this disease. So it’s not only low levels of C one inhibitor, but it’s also, you know, the triggers. And if you’re taking a capsule a day, versus thinking about, oh, I’ve got to infuse, or I’ve got to inject or I had an attack, and I got to treat it, that’s stressful. And so that that may be a contributor as well.
Brian Abrahams (RBC Analyst): Got it. There’s clearly a large opportunity as well amongst undiagnosed or even diagnosed, but untreated HAEd patients in the US, can you talk about how important this is for long term growth? And maybe the types of educational efforts you’re pursuing around this?
Jon Stonehouse (CEO): Yeah, that’s, that’s not the data, we see Brian. In fact, the, the market research that Charlie did a couple of years ago said, this is a very mature market, you know, 7500 patients diagnosed and treated that HAE Association says the same thing. And I guess our competitors would say the same thing. So it’s, it’s a very mature market. So this is not find the patient’s Japan is a different story. That’s a fine the patient market. So here, it’s all about switches. And you know, and again, I think some people in the investor community didn’t believe that we had the efficacy to get people to switch but an an oral wasn’t enough. But that’s what we saw in the market research. That’s what we saw in the clinical trials. And now we’re seeing in the marketplace. And so it’s a switch market.
Brian Abrahams (RBC Analyst): Okay, that that’s really helpful. Um, what about the European market? What do you need to do to establish this market, which is been historically, you know, less prophylaxis oriented? And what kind of, I guess, initial signals of uptake? Should we look for there?
Jon Stonehouse (CEO): Yeah, Charlie, I’ll start. And then you can get into some of the specifics answering Brian’s question, but I mean, first off, it’s pretty amazing that a company our size, you know, filed in major territories around the world, and in a matter of six months, got four approvals, right. I mean, that that in itself is pretty remarkable. And our goal, that’s part of our strategy, right, take the data we have, and go country by country around the globe, and continue to get approvals because our belief is, you know, every country that can contribute 5-10 million dollars, is going to add to that goal, that we have a $500 million plus global peak sales. So Europe’s an important piece of it. It’s an efficient way to get into the market. And I’ll let Charlie talk about the differences in that market, and also our approach.
Charlie Gayer (CCO): Yeah, and so Brian, we’re taking a similar approach is to the US and that we we brought on really experienced commercial teams who really know how to launch drugs and have a real passion for rare disease. And so the first the first launch, you can expect is Germany this this quarter. And, you know, I think that historical, what we’re hearing from physicians and patients is the historical limitation and prophy was really due to lack of available options. That started to change with the launch of text IRA a couple of years ago. And what the HAE specialists tell us is that they anticipate increasing profit over, you know, up to an over 60% of their patients in the future. And so starting with Germany, you know, that’s a change that we’re going to drive, we have Early Access Programs in France and the UK. And as John said, we look, we look forward to going all around Europe. And we think that we have some great opportunities there.
Brian Abrahams (RBC Analyst): It’s great. That’s what kind of pricing power we’re expecting Europe.
Charlie Gayer (CCO): So we’ll announce our German price when when we launch I think what I can give you as just kind of a framework right now, look at the takhyzro. Price in the US the whack is about $590,000. And in Germany, their final price is around $360,000. US dollars. And so that at least gives you a framework and then as we launched, we’ll announce our prices in the different markets.
Brian Abrahams (RBC Analyst): Got it. Great. Maybe shifting gears to the pipeline and 9930 you outline two pivotal studies will be starting the back half of this year. Can you talk a little bit more about their designs and how they were shaped by the emerging proof of concept data that you’re seeing out of that program?
Helen Thackary (R&D): So our goal is to achieve a broad label as an oral monotherapy for All patients pnh, our phase one data it will be successful at that. We’re moving directly from phase one to pivotal trials based on that data. And the program is moving very quickly. In terms of the designs, we’ve agreed with the FDA on the basic design and the primary endpoints, the endpoint will be changed from baseline and hemoglobin for both trials, we’ll have two trials, one in patients who have who are not on C five inhibitors and one who are on C five inhibitors and are having a poor response. And that it will be oral monotherapy. In both trials, we know the dose which is 500 milligrams. And so as we proceed into initiating those trials, we’ll get more details on protocols.
Brian Abrahams (RBC Analyst): Got it. For the study in this sea five inadequate responders, I guess what have you learned from your ongoing work, the mechanism studies, maybe others have done in disease pathophysiology. to shape your confidence there were I know there isn’t directly proof of concept yet.
Helen Thackary (R&D): So we have in our phase one data, but it’s given us tremendous confidence, as I said, and the data shows outstanding control for monotherapy. And so that control is for primary oral monotherapy. And it has control for hemoglobin, and increasing hemoglobin and it’s control of the need for transfusions. So we with that we have all the data we need to move to pivotal trials. And the FDA agrees with that. There’s there’s no difference in disease state for patients, regardless of their therapy, whether they’re on C five inhibitors or they’re not their disease state is the same. And so proximal inhibition is an appropriate method of controlling the disease. And that’s that’s what we think that’s what we doing both of those trials. So our, our protocol with in phase one does allow for capturing data with withdrawal of C five inhibitors, but we have the information we need to proceed with that in pivotal trials.
Brian Abrahams (RBC Analyst): Got it. as you alluded to 9930 has shown strong effects on on hemoglobin and transfusion, it’s stronger effects on those parameters versus on ldh. Can. Can you talk about your regulatory feedback on this front? And just the importance of outcomes and patient level measures to the agency in the field relative to your biomarkers, maybe older biomarkers like ldh. And I guess what are the other key secondary endpoints of the phase three that are going to be important beyond the hemoglobin primary?
Helen Thackary (R&D): Yeah, I would actually start with that point on ldh. It is a biomarker. It’s an older biomarker, it’s been a surrogate endpoint, it’s not a clinical measure. The clinical measures are the ones that matter when you’re achieving disease control. And so change from baseline and hemoglobin is a clinical measure and infusions are clinical measure, we’re seeing strong differences and both of those in our data. And those are been our primary endpoints. And that in terms of feedback from the agency, we have clear alignment with the agency that those are the appropriate measures for proximal inhibition, there are the appropriate measures for clinical control. And so I think there’s really no question around that, we will be assessing secondary endpoints, and we’ll be looking at biomarkers like ldh amongst our secondary endpoints. based on the data that we’ve seen in our phase one, we’re very confident on our ability to hit the primary in both in pivotal trials.
Jon Stonehouse (CEO): I think another thing to Brian is, payers are going to be interested in you know, transfusions, and the lack thereof. And so that’ll be an important piece in discussions on pricing and the like when we get approval.
Brian Abrahams (RBC Analyst): Got it. What’s your level of confidence in your ability to enroll a treatment naive can age study? how challenging might that be? And what are some of the strategies that you can take things like, you know, global sites or what not, that could enroll a study rapidly and with a patient population that could be adequate to the FDA to facilitate us approval.
Helen Thackary (R&D): So we’re competent, first of all, and this the these will be global trials, so we have access to patients around the globe. We’ve also successfully enrolled in our phase one during a global pandemic. And so to us, I think we are really quite confident in our ability to do this going forward in both populations, and so really, you know, something that we’re
quite happy with
Jon Stonehouse (CEO): I’d add too, you know, in the HAE program with Orladeyo. We had sites all around the world for our Apex s study. So it’s not like this is new to us.
Brian Abrahams (RBC Analyst): Great. Can you touch on any other areas beyond pnh? that you’re interested in pursuing with 9930? What are your latest thoughts on other indications that could be leverageable? For what what are you most excited about prioritizing?
Helen Thackary (R&D): So this is a, this is a really exciting area for us. We have a, you know, effective factory inhibitor that we’re taking into trials and in pivotal trials, and P and H, it is, as the results were something that we will then look at as for proximal inhibition and other alternative pathway diseases, we’ve talked about a renal path and proof of concept and renal diseases and select complement mediated nephritis indications are an appropriate place to go. There are other diseases where the alternative pathway is critical to the biology and to the clinical outcomes in the disease. And so I think there’s several places we can also look following that. And and I think one thing you’ll see with us is taking a world monotherapy into treatment for the alternative pathway is something that gives us a potentially very wide reach with this drug. So more to come.
Brian Abrahams (RBC Analyst): look forward to that. And maybe just in the last couple of minutes we have remaining on the 9252 program, where do you guys stand now with respect to some of the ongoing non clinical work there in terms of product tox, manufacturing, etc? And what are the key factors gating factors for phase two initiation?
Helen Thackary (R&D): So are we are progressing and making progress. So we have nonclinical and tox work to do in manufacturing to do to advance the phase two that will take most of the year to complete. And we’re proceeding. with that. I think well, we’ll proceed from there into phase two trials. And we’ll update later in the year. I don’t know, john, if you want to add anything else on that?
Jon Stonehouse (CEO): Yeah. This is a high high unmet medical need, right. And there was a period of time where it looked pretty crowded, that there were going to be a lot of drugs that were going to come to the market and, and then a bunch of them didn’t make it. Right. And so, you know, we didn’t invest in parallel like we did with 9930 in complement mediated diseases where we’re running talks and drug supply manufacturing, in parallel. So now we’re playing catch up. But from our perspective, right now, there’s still a huge unmet need for patients with fop. And we’re going to move that as quickly as we can, but we got some ketchup to do.
Brian Abrahams (RBC Analyst): Understood, and any comments on sort of how that when that does move into phase two, how you envision that clinical development program?
Jon Stonehouse (CEO): I think at this point, it’s, it’s, it’s hard to predict. I mean, it this is a disease The earlier you catch people, right kids, the the better, but you know, in all drug development, you got to start you can’t start there. And so, you know, we’ll have discussions with regulators and just like we have with every other program and figure out what the best path forward is.
Brian Abrahams (RBC Analyst): That makes sense. Well, great. Um, I know we’ve covered a lot. Unfortunately, we’re just about out of time. So john and team thank you guys so much for presenting and being a part of this and look forward to talking again soon. Thanks. Thanks to the audience for listening.
Jon Stonehouse (CEO): Thanks, Brian.