Okay, I think we're going to go ahead and get started with our next presentation. My name is Chris Raymond. I'm one of the biotech senior biotech analysts at Piper Sandler. Pleased to introduce our next presenting company, which is BioCryst Pharmaceuticals. We've got with us the CFO, Anthony Doyle. We've got about 24 minutes or so for Q&A, but just a quick logistics and housekeeping announcement. This is a fireside chat, so very informal. If anybody in the audience has any questions, please just raise your hand. I'll make sure it gets asked and answered. I've got a ton of questions here for you, Anthony.
If maybe first you could just provide a little bit of an update for investors who aren't completely familiar with the BioCryst story, maybe the elevator pitch, if you will.
Sure.
And then we'll dive into Q&A.
Sure. Thanks for having us.
Sure.
So just as a reminder, we might be making some forward-looking statements. Those statements have risk, and you can find our risk factors on our website. So BioCryst has been around for a while. Most notably of late, though, we have an oral drug available in hereditary angioedema, which is a rare disease. Here in the U.S., there's around 7,500 patients. It manifests itself in swelling events.
They can be fatal. Up till about 10 years ago, there were no drugs available. There's about eight now on the market, mostly historically acute and then most recently, prophylactic. When we entered the market in 2020, it was solely injectable drugs that were in the market. We are an oral once-a-day capsule. The launch has been going phenomenally well, despite COVID.
I think we've been asked previously if there are analogues that people should use when they're looking at our drug launch, and I think the answer has or is becoming that we should probably be an analogue at this point. It has been a great launch thus far in a hard market.
There's, like I said, multiple other drugs available. But the steadiness of the launch, the steadiness of the revenue generation, the patient adds that we have seen, and the expectation that that will continue on its way to being a billion-dollar drug, has been fairly phenomenal. Behind it, we have a pipeline. We had recently an R&D Day down in our biotech center of excellence in Alabama, where we announced five new molecules on top of we already have a Factor D molecules in development.
And so the strength of the financial position we're in, the strength of the launch of ORLADEYO, and then the depth of that pipeline, puts BioCryst in a really great spot.
Yeah, excellent. That's a great setup. Yeah, to your point, using ORLADEYO as an analog, not too many examples maybe of a successful, you know, launch in the teeth of COVID, with a new mechanism, a new therapeutic modality in a disease with a number of entrenched competitors.
Yeah. Yeah.
So maybe let's just talk a little bit for folks who might not be completely familiar with the HAE story and the market and the opportunity. You've got an acute and chronic dynamic. Just to give investors maybe, if you will, a little bit of a background on HAE. R eally how ORLADEYO has sort of transformed, you know, the treatment, you know, decision tree, if you will.
Yeah. So like I said, here in the U.S., about 7,500 patients diagnosed and treated. New entrants to the market have been relatively recent, so patients remember when there was nothing on the market. What that has led to is a high level of stickiness in the market, where there's a lot of... When we talk about switching patients from prophylactic treatment onto another, there's a lot of, "If it's not broken, why fix it?"
And honestly, when we go in and we talk to patients, we talk to doctors, a lot of it is around the fear of: I have something that works. I didn't previously. I remember having a lot of attacks. These attacks can be fatal. So as much as something might be better, I just don't want to risk it. So there's three injectables on the market for prophylactic treatment.
We are the only oral on the market. What we have heard from KOLs and doctors is that they love choice, right? They really enjoy having multiple products in the market to treat prophylactically these attacks, and that oral, an oral solution has been life-changing.
So whether it's people who just don't want to use needles or, you know, don't want to store it, cold storage, and have to travel with it, the opportunity to be able to treat their HAE with a once-a-day pill has been honestly life-changing for a lot of the patients. Now, what we've said is that none of these treatments that are available are perfect, and so there's always going to be acute treatments that are necessary in the market.
But to your point, doctors are more and more moving towards utilizing prophylactic treatment as the best treatment for patients. If you can avoid these attacks, it's better to avoid them than to treat them. So we've been, I think, welcomed into the market. We've had a really strong launch. In the first year, we did about $120 million in revenue. Second year, $250 million. No less than $320 million this year, on our way to $1 billion expected at peak. So I, I think both from the patient population and the KOL population, a very welcome addition to the market.
So maybe on the commercial, to continue on the commercial line, you, you guys had a, you know, pretty significant milestone recently. You crossed 1,000 U.S. patients in early May. Just maybe, I know you probably don't want to give a blow-by-blow as to, you know, okay, so now we're at, you know, 1,020 or whatever. But, what is... Can you give us a sense of the velocity of that patient number going forward, and how are there other waypoints that you might provide in terms of patients on therapy?
Sure.
Yeah.
Yep. So, yeah, we passed 1,000 patients on therapy here in the U.S., which was phenomenal. Kind of three years into the launch. Or less than three years into the launch. It's been very steady.
Mm-hmm.
So there's not necessarily a dichotomy, but there's a difference between the trajectory that we've seen in terms of net patient adds and the correlating revenue, right? The first year was all about getting. In addition to getting patients on drug, it was about getting coverage. And so there was a little bit of a disparity there that needed to be caught up with.
Over the last two years, we've seen them be more in line, but Q1 has issues around reauthorization, for example, co-pay assistance, resets, et cetera, right? There's going to be a dynamic whereby Q1 is lower, Q2 is higher, Q3 and Q4 are more normalized. But overall, we've gone past 1,000 patients. What we're looking to is the future.
And so at peak, which will be later in the decade, our hope is that we'll have north of 2,000 patients. And from a kind of simple math perspective, we're looking at adding about 200 net new patients, so that's new patients net of discontinuation, during that timeframe.
We announced in our, I think it was in our Q1 earnings call, that we had added about 300 patients in the time period that was preceding those trailing 12 . So on an average basis, given the steadiness of the growth that we've seen, if we can add about 200 new patients for the next few years till we get to the peak, that's our path to that's the major lever for how we get to that $800 million that would be part of the billion-dollar peak here in the U.S.
Excellent. Thank you for that. So, another lever obviously is to mitigate the discontinuation.
Yep.
I know you guys have talked, you know, pretty openly about the discontinuation rate and the commercial steps you're doing to sort of mitigate that. But maybe just give an update on how the discontinuation numbers, for, again, for the folks who might not understand the story, how it was at launch. I know the dynamic of explaining to patients to wait it out. There's clearly a benefit for patients to stay on drug. You know, the key reasons are GI tox and also, you know, perceived lack of efficacy.
Mm-hmm.
Maybe just talk about the efforts you guys have made commercially to sort of tell that story, and what are the results? How are things? Yeah.
Yeah. And I'd break it down to your point. You know, for patients who are new to ORLADEYO, within a 12-month period, the retention rate's around 60%, so DC is at around 40%. That generally happens early, so within the first two to three months, and generally for the two reasons that you talked about, so perceived lack of efficacy or GI tolerability.
For patients who remain on ORLADEYO north of 12 months, it's a really, really sticky drug, so the retention rates become really high. So when we're thinking about getting into the latter part of the decade, where we're looking at this ever-building population of patients who are on drug, the average of that discontinuation rate gets lower because of the high level of population of patients who are on drug.
Then still, for any patients who are new to drug, 60% is a good number for patients who remain on during that time period. In terms of what we've been doing, so just a high level of education. So we use a sole source specialty pharmacy, so the level of access to data that we have is high.
Whether it's kind of doctor data, regional data, correlation to insurance, patients who are on commercial insurance versus Medicare, Medicaid, et cetera, we have a really high level of access to data. What we've been doing is working with our scientific team to make sure that from an education perspective, especially around the GI, for example, is that patients are giving ORLADEYO a fair try, right?
If, if there are GI side effects, they're generally tolerable or will dissipate within X number of weeks or months. And once they go away, then they generally stay away. So for patients who weren't expecting to see GI impact, to make sure that they have the education, that they are going to have... They, they could well have some issues.
And if you have them, here's usually how they manifest, and if you treat through, you come out the other side, in the clear. That's been received well. I think if it comes as a surprise to you, that's not a good thing. For those who are then ready for and know how to treat and what to expect... We've seen a lot of movement in terms of having patients stay on for longer and give it that fair try.
In terms of perceived lack of efficacy, listen, the drug doesn't work for everybody. We've been clear about that through the clinical trials. We've been clear about that through real-world evidence that we have seen. But for those who it does work, it works really, really well.
And so again, given that things like stress can be trigger events for HAE attacks, trying to make it easy for patients to get on drugs, stay on drug, et cetera. Making sure that they know that these stressful times can bring on attacks, and that might not necessarily be due to a switch or a change of your medication. Just making KOLs, doctors, and patients more aware of what to expect during that time period, I think has paid off really well.
Awesome. Okay, so you guys have been very consistent about your peak billion-dollar guidance, with what, 80/20 U.S. versus ex-U.S.
Yep.
You know, even with you know, some changing dynamics in the competitive landscape, you've had some players that have fallen by the wayside. There's, however, also another oral therapy that's in development, you know, for both prophylactic and on-demand. Maybe just talk about you know, why you remain confident in that number, you know, especially given that competitive effort that's out there.
Yeah.
Yeah.
So every drug that has come to the market, and I think every drug that will come into this market, is going to have to be differentiated in some way, shape, or form. For us, that biggest differentiation was obviously the oral factor. But again, back to this idea of, efficacy and... Patients won't sacrifice efficacy for convenience, and so if the drug doesn't work for them, they won't stay on ORLADEYO, and that's, that's absolutely fair. But for those who it does work, it works really, really well.
So what we try and look forward to is: what is the product profile of these other orals? What will they—how will they differentiate? What will they bring to the market if and when they get launched? And I look forward to that and where will we be at that point in time, right?
They're not going to get approved next year, so it's going to be some time, at which point we'll continue to be advancing towards peak. And that patient population who stay on ORLADEYO are well treated, well tolerated, and are seeing a significant improvement in quality of life in terms of the attack frequency that they see.
So going from a once-a-day oral to either one, another once-a-day or twice-a-day, which some of the profiles of the competitors are, is it going to be efficacy? Well, if you're well treated and you're seeing a significant reduction in the number of attacks, or you're having no attacks on an average basis, what would the profile have to be for those drugs to get you to move?
Mm-hmm.
And so I feel like at that point in time, we'll be really strongly placed. And will there be a place for those other drugs? Probably, right? We talked about there's a 40% discontinuation rate, which means there's patients who want to try oral, want it to work, and ORLADEYO hasn't been that drug for them. So might it be one of these other drugs? Yes. But do I think they're going to take a significant market share away, given the product profile that we see at the moment from ORLADEYO? I don't think so.
Okay, excellent. So maybe just on the, on the prescriber mix, I think you... I've heard you guys talk about more than half of prescriptions coming from the top 500 doctors who prescribe, and then, you know, you've got the others, you know, very classical concentration of prescription.
And I think you've said on top of that, every quarter, you're seeing a consistent number of new prescribers. Just, you know, what is the dynamic there in terms of, you know, what's a steady state to getting... You've given the patient numbers that you're hoping to attain to get to the peak revenue number, but, how does the prescriber dynamic sort of dovetail into that?
Yeah, it continues to get better quarter-over-quarter. And so given the frequency or infrequency of how often some of these patients are visiting their doctors, whether it's once a year or twice a year, it's not very frequent, and so the opportunities for patients to change drugs, change medications, make a switch are, are not very frequent.
But we have been continuing to adapt and make changes within our own company. So I think we have a, a very robust organization in terms of the territorial view, the regional view, the individuals that we have who are medical scientific liaisons, patient assistance individuals.
But we did make some significant changes at the tail end of last year, where we enhanced the number of territory or the number of regions that we had, and then we added to our workforce of people who are supporting the medical and scientific side and then the patient access side.
Mm-hmm.
So we've continued to enhance and increase the number of touch points that we have with individual doctors and then enhance the breadth that we have in terms of the number of doctors that we can reach out to on a frequent basis. And so the steadiness of the growth that we have seen is not limited to the number of net new patient adds, but also the prescriber base that we've seen.
And we feel confident that there's still a significant amount of work that we have to do, right? There's still a significant amount of prescribers who are either not prescribing ORLADEYO or not to a significant amount of their patients. And so from an opportunity perspective, we view that as a good thing.
So let's talk about the pediatric opportunity. I think, b eginning of this year, you began enrolling APeX-P, which is the trial evaluating on the pediatric patients. Maybe talk about the. I think you've guided to the sBLA being filed in 2025.
Mm-hmm.
Just maybe talk about the setup there, the opportunity- h ow that plays into the billion-dollar, you know, peak guidance, and sort of, you know, as we see, you know, 2025 and 2026 play out, what kind of inflection you might be anticipating from that new indication?
Yeah. So first and foremost, I think it's very important for the patient population, right? At the moment, there are approved drugs for that age range, but it's injectables again.
Mm-hmm.
And so not only did we look at taking ORLADEYO into that space, but we reformulated it, so it's not a capsule. It's granules that can go on, can be added to food and that children and earlier age individuals can take relatively easily. Population-wise, it's not huge. Maybe there's 500 patients. I do think from a first-line perspective, that would place ORLADEYO really well for that age group.
The trial has been enrolling really, really well. There's been a lot of demand within that space. And so getting to the point where we can get ready for submitting an sNDA in 2025, I think is very realistic. I think we can penetrate that market really well and offer something that that group of individuals and their families are looking for.
In terms of the dynamics of the trial itself, we're looking for PK data, and we're looking for safety data. It's weight-ranged cohorts of individuals, and across the board, again, enrollment's been going really well.
Okay, great. So, we've got about four minutes or so left.
Sure.
I want to talk a little bit about your pipeline. You guys had a, you know, fairly involved, almost watershed, you know, R&D day, a few weeks ago. You highlighted a variety of new assets, at this session. Maybe just walk us through some of these newly disclosed programs.
Sure.
Which ones, you know, you feel most excited about, and why. You know, there was very little reaction to the stock. I know, you know, unveiling new programs rarely moves the stock, but, you know, what are people who might not be paying attention to these programs... This is a long-winded question, sorry.
No, please.
What, what are people not paying attention to that they should be paying attention to?
Yeah. So in addition to the ORLADEYO peds, and then we have BCX10013, which is our Factor D molecule, which will have a proof of concept readout next year. The R&D day was great. I mean, we've been working on these assets for quite some time, and so being able to unveil them was great.
In terms of how to group them, so there's two in the protein therapeutic space, a KLK-5 inhibitor and BCX17725 for Netherton syndrome, and then a bifunctional treatment in the complement space. What I'm most excited about in that area is the ability for BioCryst to diversify out of only being looked at as a company who develops oral small molecule molecules. So I think in terms of the diversification of risk moving forward, that's great.
Then looking at the oral side, you've got a C2 and a C5, which are, I think, very big or very high unmet need areas with very substantial markets associated with them. C5 specifically, C5 is in a space that's scientifically validated, right? There are drugs on the market, and that C5, the mechanism of action works. So if we can get an oral solution into that space, that's very exciting for us.
And then on the DME side, so avoralstat, which was, you know, a drug that we tested for HAE, and didn't, you know, didn't move forward. ORLADEYO won the day there. But part of the reason it didn't work, it was, you know, wasn't very orally bioavailable and, from a solubility perspective, wasn't where it needed to be.
But for a disease state like DME, if we can inject, we partnered with Clearside to get access to their suprachoroidal injector. If we can inject that into the right space of the eye and have it sit there and not be massively soluble, such that we can have an infrequency of dosing, and not in a space where we're looking to be first line, like that'll be the anti-VEGF.
But to give patients there an opportunity to have a different type of treatment, that's exciting too. And it's not rare, right? It's rare in terms of the way... or it's rare adjacent in terms of the way that, there's a concentration of prescriber bases and doctors who would prescribe the drug, but it's not rare in terms of its treatment. So that's another one that's super exciting.
Okay, excellent. We've got time for maybe one more question.
Sure.
I saved the best for last. It's maybe a couple of CFO questions.
Cool. We can do that.
Part one and part two of it.
Yeah.
One more question. So just talk a little bit about the cash, you know, runway. You know, with our new development programs also comes new spend, right? So, talk about... You, you got the benefit of having ORLADEYO, which is a, a, a really nice offset to, to spending, but, you know, in terms of, you know, the holy grail of cash flow positive, you're, you're a ways off.... How are you balancing, you know, the source of cash, needs for cash?
Yeah.
And keeping you know everything on the up and up- as you need to do.
No, I mean-
Job one for you, I'm sure.
It's a big thing for us, right?
Yes.
So $400 million, give or take, in cash on hand. We have access to another $150 million in debt, should we so choose, to pull it before September. And like you said, growing ORLADEYO revenues. So looking at capital allocation and making sure that we are being very thoughtful, very protective, of that cash, especially in this market, which is terrible, is of foremost important to us.
We do have, like I said, with BCX10013, a proof of concept readout, so that'll inform us as to whether we're moving forward into pivotal trials or if we don't have proof of concept, does that program get terminated? Which I think will be a big deal for us next year.
But the rest of the early-phase molecules are just that, they're early phase, and so the required investment in them is going to be, you know, not a huge amount in the grand scheme of things, especially when I compare it to the BCX10013 program. And if I think about how we go through milestones from there through proof of concept, at every step along the way, we got to make sure that those assets are either best-in-class or first-in-class, and if they are, we'll move forward.
If they're not, we won't. For how we fund them, yeah, the cash on hand and then ORLADEYO is an important factor in terms of the revenue generation. But there's other opportunities that we'll have out there, and that includes elements like partnerships.
Like, if we can't move them forward and they're best-in-class and first-in-class, and somebody else with the capital to move them forward, then we're absolutely open to go on that route. And if they are best-in-class, first-in-class, then I don't think there will be any shortage of people who want to move them forward. I think we're really well capitalized. We'll be very smart about the capital allocation and make sure that not only are we advancing the pipeline, but pushing ORLADEYO to that $1 billion.
Awesome. Great. Well, lots going on. Thanks for the presentation. It was great.
Yeah. No, thank you, guys.