Great. Well, thank you, everyone. I'm Andrew Fein. I'm one of the biotechnology analysts at H.C. Wainwright. It's my pleasure to have BioCryst present next. It's Anthony Doyle, the company's CFO. So maybe the best place to start is with ORLADEYO.
Sure.
You know, obviously, you recently reported first quarter sales. You know, you continue to surprise to the upside, I think, relative to investor expectations. Maybe you can talk about, you know, the drivers of growth from here, and how you see things kind of working going forward.
Yeah. Thanks for having us. So as a reminder, we'll be making some forward-looking statements. Those statements have risk, and you can find our risk factors on our website. So Q1 was a great quarter for ORLADEYO. We had 30% growth quarter-over-quarter from Q2... Q1 of 2023 to Q1 of 2024, and the biggest driver there is the demand for the product. So the commercial team has done a phenomenal job, specifically here in the U.S., of getting net new patient starts for the product. For last year, we had about, I think it was 321 net new patient starts. And so the vast majority of that, growth, that 30% is driven by just that performance, coupled with, the steadiness that we see in terms of the retention rate.
Specifically in Q1, we did have a tailwind related to the speed at which we moved through the reauthorization process. That's, you know, a Q1 dynamic that plays out every year, and the team has continued to do a great job around learning more, working with patients, working with doctors to try and move it as fast as possible. And, you know, again, the speed at which they were able to do that led to... We were calling initially $85 million for the quarter, and we landed at $89 million, so that $4 million growth is predominantly driven by that. In terms of from here on out, the biggest driver is gonna continue to be patient demand.
Both what we've seen historically and what we continue to see in terms of the market research that we do leads us to believe that, you know, from doing $390 million-$400 million this year, the path to $1 billion plays out primarily driven by that patient demand continuing from, you know, both existing prophylactic treatment users and, and acute users. But coupled with some improvements that the team can make in the next couple of years around the free-to-paid drug and, you know, then some minor price increases along the way, but predominantly driven by new patient demand.
What does your market research tell you about, you know, where the patients are coming from, and what’s influencing their decision-
Yeah
... about choosing ORLADEYO? And maybe the derivative of that question is the reasons behind their choosing ORLADEYO, is that likely to yield increased stickiness in the light of, you know, new therapies down the road?
Yeah. And so ORLADEYO is the only oral prophylactic treatment for patients with HAE, so for patients who are looking to either switch from an injectable to an oral because they want to see efficacy that's just as good, but with the convenience of a once-a-day oral, or whether they are using rescue or acute medication and have worked with their doctor to determine that prophylactic treatment is the right solution for them, minimizing the number of attacks that they have, as opposed to just dealing with them as and when they occur. That's the... You know, we've seen 50% historically come from prophylactic switches, 50% come from new patients who are new to prophylaxis. What will we see going forward? We have market research that says it might be more heavily skewed to prophylactic switch on a go-forward basis.
That hasn't yet proven out in what we've seen. We continue to see new patient growth kind of be 50/50 for those two markets. Why are patients switching? Because the drug works. We've been clear on what we see in terms of retention rates. ORLADEYO does not work for everybody. For those patients whom it doesn't work, they generally drop off within the first kind of two, three months, definitely within the first 12. But for the patients who it does work, it works really, really well. We have real-world evidence showing that it works as well or better than what those same patients were seeing for other injectable treatments. Patients will not sacrifice efficacy for convenience, but with ORLADEYO, they have the opportunity to get both, and I think that's the biggest draw.
Is there enough data at this point to find uniformity of any sort in the sorts of patients that don't respond well versus the ones that do respond well, or is it continues to be heterogeneous?
Yeah. I wish, you know, I wish there was an assay or a test or something that on a more narrow basis could determine who's gonna have success or not. But what that leads to is us pushing that everybody should try ORLADEYO. If you have the opportunity, and again, 60% retention rate, if you have the opportunity to be in that cadre of individuals for whom it really, really works, we would encourage all patients to try it.
When it doesn't work, I suspect there are degrees of it not working.
Sure.
You know, for some patients, you know, bringing the number of attacks down by even a small number is probably beneficial, where other patients might be more sensitive, I suspect.
Yeah, I think it depends again on what your expectations are, where you're coming from, and how you were treating your disease previously. But again, for the most part, based on the real-world evidence, when it works, it really, really works. And when it doesn't, and again, predominantly driven by either perceived lack of efficacy, it can be GI, it can be something else, those patients tend to identify that fairly early on. And much like those patients who are remaining on drug won't sacrifice efficacy for convenience, the patients who drop off won't either.
Mmh.
And so they'll find their place somewhere else. But I do think the more we have worked with patients, the more we have worked with doctors, the more the base grows, and the more patients and docs have experience, the more accepting they are that, again, when the drug works, it really, really works, and so there is no need to sacrifice efficacy for convenience. You can have it both.
At some point, given the infrastructure that you've built and the relationships you've built with the HAE physician community and the patient community, does it make sense to add another asset within the space? You know, does a company who has a prophylactic targeted drug, you know, benefit by also offering patients an acute therapy for their acute attacks?
Yeah.
So what's the thought process there?
I'd love to have another product. I mean, Charlie's team, the commercial team, does a phenomenal job. So I think our discovery engine, you know, the clinical side of the house and the commercial side each have value for different reasons. But giving the commercial team more, given the strength that we have seen in the ORLADEYO launch, would be a great thing. It doesn't necessarily need to be within that same space. It could be somewhere else, and I would similarly trust them within any kind of rare disease indication to do well. So whether it's the pipeline, you know, and you know, continuing to develop ORLADEYO with peds or some of the other assets that we have, the intent is to give Charlie's team more work to do.
The retention rate, I mean, you spoke about earlier, 60% or so. Can that be driven up? Are there, I guess, tactical, you know, approaches-
Mm-hmm.
that companies can deploy to perhaps see that inch upwards?
Yeah, it's a balancing act, right? The focus is, again, increasing the base and getting everybody-
Sure.
-to try it. So if that results in a continued 60%, I'd happily take that. But what we've seen is both on the perceived lack of efficacy and on the GI, educating doctors and patients as to what to expect. You know, with the GI side, it was just making sure that there was awareness that this might occur, and if it occurs, here's what you can do, here's how you can treat through it. When patients are surprised by it, that's not a good thing. What we've been excited to see is that of our new prescriptions last year, about 10% came from patients who were trying ORLADEYO a second time. And generally, it was: we think we gave up too early.
We've talked to doctors, and we've talked to other patients who have treated through one of those two things, either, you know, an attack at the start, and was it caused by the drug, was it not? We don't know. We didn't give it enough of a chance. Or the GI side effect, which are, you know, generally mild and can be well treated through, but patients want it to work, and so seeing them come back for another try has been very encouraging.
Do you have data looking at, you know, for the patients that drop off, how quickly they drop off? I guess my point I'm getting at is-
Yeah
... if you know, the initial start of any new therapy has you know, its own associated stresses, and if we know that, you know, in HAE in particular, you know, stress and-
Yeah
-an attack-
Yeah
—are definitely correlated, if patients make it through that initial period, if you will—
Yeah
-where they may calm down a little bit more-
Sure
about the therapy, does that then kind of stabilize them to the point where they tend to stay on therapy?
It can. And so again, what we've worked with doctors and patients is making sure that they give it a sufficient try, to your point around stress, right? Stress can be a major trigger. Changing your medication after a period of time can be a stressful event. So making sure that the expectation setting is there, and that if patients really want it to work, just giving it that fair try, I, I think is important. I, you know, I'd love to get to the point where we can generate some data to kind of prove that out.
But I think given the real-world evidence that we've seen and the patient populations who've gone through and treated through, you know, some of that earlier period and come out the other side in a good spot, anecdotally, yeah, I'd like them to give it more of a try than less of a try.
I mean, in oncology, I guess we've seen quite often that, you know, response rates at kind of the major centers are sometimes better-
Mm-hmm
... especially with new kind of targeted oncology agents, because the physicians there are more comfortable kind of dosing through that initial period where things pop up and getting them to appropriate levels, so you get greater benefit long term. Do you also see any correlation between physician comfort, kind of, you know, having more experience with the drug and, you know, those that are kind of able to talk patients through that initial period into perhaps yielding a longer retention? And I ask that in light of the fact that, you know, going back to the oncology analogy, you know, some companies have had good success having kind of those physicians then teach-
Sure
-their peers-
Yep
to kind of yield
Yeah
greater retention at a broader number of centers.
Yeah, the interactions that we have with doctors are kind of tailor-made to the individual, and so the messaging to, you know, somebody who treats and maybe is an academic, it might need to be different than, you know, a community doctor who treats less patients. Generally, we haven't seen any kind of major dynamics that would lead us to believe that any one is more successful than the other. But overall, having more conversations, setting better expectations for both the doctors and patients, does generally lead to better outcomes.
That's very helpful. Maybe you can speak a little bit about, you know, reimbursement and reauthorizations. I mean, you spoke about the success you had, which manifested in the strong 1Q number, in terms of having things, the reauthorizations done very efficiently-
Yeah.
This year.
Yeah.
I guess, anything else you can do kind of going forward that can manifest in future quarters?
Yeah. So if you kind of break it down into the commercial and then the government side of the house, on the commercial side, there's always things we can do. We can work with PBMs, insurers, sub-plans, making sure that they understand the benefit of ORLADEYO...
Mmh.
You know, both in terms of the benefit to the patient, and then the reduction in resources needed in the healthcare system in general, due to treatment of prophylactic, and especially a prophylactic treatment that works. So on the commercial side, there's continued work that we can do, but commercial coverage is, you know, 80% there, thereabout, so we can make some changes, some improvements. On the Medicare side, a lot of it comes down to what we'll continue to see. We have a strong approval rate, and the reimbursement rate has struggled in the last couple of years, mainly due to affordability and how much the charitable foundations can continue to supplement and help patients cover their out-of-pocket maximums.
With the implementation of the Inflation Reduction Act this year, going to $3,250, but still in one fell swoop from a payment side, going next year to $2,000, and then being able to spread over 12 months. Our hope is that affordability, both for individual patients and then, you know, the funding that those charitable foundations have and how far it will go, will continue to, you know, enhance the affordability of the product.
To what extent is cost still driving patient usage of therapies in the space?
It's mostly on the Medicare side. Yeah, it's still... It's not better than it was last year, but it's no worse. You know, last year in Q1 of 2023, I think that's what the HAE highlighted was, you know, a crisis as related to funding, which led to us stepping up to the plate and making sure that patients had access to free drug, right? We wanted to be able to do that for the community. On a go-forward basis, though, we hope that we can kind of get back closer to where we were and closer to where we are on the commercial side.
As you go to these various investor conferences, you know, because of your success, your commercial success, you invariably get questions about, you know, competitive dynamics in the space. You know, companies, you know, with drugs in development, many of which have yielded positive data.
Sure.
You know, of course, there's a step between the positive data and commercial success-
Yeah, yeah.
- As you guys well know. And it can go both ways, right?
Sure.
So, how do you address those questions broadly, in terms of, you know, you'll never be able to satiate, you know, the entirety of, of-
Yeah
... hypothetical concern? But to the extent you can, how do you, how do you address-
Yeah
... the questions that come up?
I look at the profile of ORLADEYO, and, you know, it is the only oral option for patients who want to treat HAE. And so as new drugs come to market, what is the differentiation that they're going to have versus other drugs in the market, including us? When I look at the real-world evidence that we've been able to generate, showing that, again, ORLADEYO does not work for all patients, but for some- those who it does work, it works as well or better than other treatments that are available out there. So as and when these entrants get to market, what is the profile that they're gonna have that's gonna displace, right? I believe that it's gonna make it harder for us to get kind of new patients, but, you know, maybe that's out in kind of 2027, 2028.
As we're talking about, you know, some of those entrants getting to market, at which point in time we'll have had an eight-year head start, have built a significant base. But for a patient who's well-treated on ORLADEYO, you know, let's look at the oral for a second. What is that oral gonna have to do to displace and get access to those ORLADEYO patients? I just don't think it's gonna be differentiated enough. ORLADEYO works really, really well in those patients who it doesn't work. For those patients for whom it doesn't work, that's a great opportunity for them. But for the patients that it does work, this idea of kind of stickiness and, what we're seeing in terms of the fight that we have to get patients off other treatments onto our drug, can play in our favor.
I think we are and will continue to be very well placed within that market.
That's a good answer. Maybe in the last couple of minutes, we haven't spoken about the pipeline.
Sure.
but there continues to be-
Mm-hmm
... active discovery and pipeline development. So maybe you can speak to the efforts there.
Sure. So I think the most imminent of which that I'm excited about is the pediatric indication for ORLADEYO, and so having a targeted treatment for, you know, children aged 2-12, who currently have access to an injectable. You know, we looked at it and said, "Great, we think we can give them an oral," but I have young kids. Having them swallow a pill can be, you know, difficult at the best of times. So having a targeted treatment that is a granular formulation that they can use like sprinkles and put on liquid or food, whatever non-acidic substance that they have, can make things easier to treat those kids, where sometimes what we're hearing is, you know, the cure is worse than the disease, and people are treating attacks as and when they occur too often in the pediatric indication.
So the opportunity to have a, you know, a filing event next year is really exciting for, for ORLADEYO peds and the expansion of that label. Outside of that, yeah, we have a, a data readout on ten 10013 , so we'll either partner or, you know, terminate that program, depending on how those discussions go with potential partners. And then into the clinic with KLK5 for Netherton syndrome, tail end of this year, and then with avoralstat for DME next year, and then thereafter for C2 , C5 , and a bifunctional. We're looking at making sure that the risk profile of that pipeline is kind of broad enough, but tailored enough, right? There's a, there's a balance.
You can imagine that if we have 5, there's more than 5 that we initially had, and we've worked to make sure that we're only looking at those assets that we think can be best or first in class or both. KLK5 has the opportunity to be both. The DME asset has the opportunity to be very competitive in, you know, against kind of VEGF resistant patients, if it works, and, you know, we'll know soon enough, right? The focus is balancing, getting to and through profitability, while continuing to develop that pipeline and coming up with the next ORLADEYO. Pipeline's in a really good spot.
Great. Well, I think we're all out of time, but thank you very much-
Yeah
... Great, very great talk.
Thank you, Andrew. Thanks.