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Wells Fargo Securities Healthcare Conference 2023

Sep 6, 2023

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

All right, I think we'll get started here with our next fireside discussion. So, my name is Derek Archila. I'm one of the Wells biotech analysts. Next up, we have BioCryst. From the company, we have Anthony Doyle. He's the CFO. Anthony, thanks so much for joining us for the discussion.

Anthony Doyle
SVP and CFO, BioCryst

Yeah, thank you for having us, and just as a reminder, I'm making some forward-looking statements, and you can find our risk factors on our website.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Gotta throw the disclaimer.

Anthony Doyle
SVP and CFO, BioCryst

I gotta put the disclaimer in there.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Um,

Anthony Doyle
SVP and CFO, BioCryst

Does anybody have that in bingo?

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Maybe just to start out, you provide a little bit of background about the company, you know, your commercial stage and maybe a little bit about your pipeline. We can dig into some of the questions.

Anthony Doyle
SVP and CFO, BioCryst

Sure, sure. So we are based out of North Carolina, and we have a discovery center of excellence in the biotech hotbed of Birmingham, Alabama. We have a commercial drug in ORLADEYO, which in its first year, did $120 million, second year, $250 million, on a path to no less than $320 million this year and onwards to a billion-dollar at peak. So a great launch thus far and strong trajectory from here. And then to your point on pipeline, so we have both pipeline in terms of our, w e're going after a pediatric indication for our commercial drug, ORLADEYO. We have an asset in which we are going after proof of concept in a PNH indication, which will lead us to renal diseases.

And then we're really excited to have an R&D Day planned for November 3rd in Birmingham, where we will unveil numerous new molecules that we are looking to bring through the development cycle. So

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Perfect.

Anthony Doyle
SVP and CFO, BioCryst

Exciting time for the company.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Indeed. Well, maybe let's start with ORLADEYO.

Anthony Doyle
SVP and CFO, BioCryst

Sure.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Well, we'll spend a fair amount of time here, but, you know, as you said, launch going very well, continues to ramp. I mean, what's kind of been the main driver, you think, of kind of the performance and as you kind of start thinking about getting to peak, right? So you're almost, like, 30% of the way there.

Anthony Doyle
SVP and CFO, BioCryst

Yeah.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

You know, how do you kinda continue to push, to get to that billion-dollar

Anthony Doyle
SVP and CFO, BioCryst

Yeah

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

You know, peak sales number?

Anthony Doyle
SVP and CFO, BioCryst

Yeah, so it's a differentiated drug. So it is an oral, once a day pill for patients with HAE in a market where, at the moment, there are only injectables. So from a burden of treatment perspective, you know, really, really well-placed. I think the first year surprised some people. It didn't surprise us, right? We had done a lot of market research and ascertained where we thought we were gonna be, so it was great to see that play out. From a trajectory perspective, that's a little bit of a slower burn. What we have seen is continued steady growth for the product. Patients are generally gonna get in to see their doctors maybe once, maybe twice, on a per annum basis. So it's predominantly a switch market.

We have seen about 50% of patients come from existing prophylactic treatments, and the remainder come from patients who are mostly using acute or rescue medication to treat attacks as and when they occur. It's been great to see the hypothesis that we had laid out prior to launch play out. I think in terms of the trajectory going forward, it'll continue to be steady growth, right? There's absolutely some opportunities in terms of free drug transition to reimbursed, but the steady growth, both here in the U.S. and then ex-U.S., as we get into more and more countries and territories around the world, is what leads us to firmly believe that there's a strong path to getting to that peak of $1 billion.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Gotcha. So maybe just kind of more on the market dynamics. So I mean, obviously, you said it's a switch market, but I guess, can you kind of frame for us, obviously, like, also new starts and kind of like where the buckets of where most of the, the ORLADEYO patients are coming from?

Anthony Doyle
SVP and CFO, BioCryst

Yeah.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Again, also, which ones do you kinda see as kind of the growth driver? I mean, is it more about, again, moving these patients who are taking acute meds maybe, you know, less frequently, not taking much unless they have some sort of attack, and getting them more on a prophy type of treatment?

Anthony Doyle
SVP and CFO, BioCryst

Yeah. It's both. So to date, it's probably been 50/50. And patients who are well-controlled on other prophylactic treatments are great candidates to be well-controlled on ORLADEYO. We've seen, you know, really good transition of those patients to successful patients of ORLADEYO, with strong retentions into the year and then even longer than that, where if a patient is gonna drop out, it usually happens within that first, you know, three-month timeframe. But for patients who've been on the drug more than a year, the retention rates are really, really high. So I think it seems counterintuitive sometimes, but those patients who are well-controlled on Takhzyro or HAEGARDA, they're the best candidates to be well-controlled then on ORLADEYO. There's still a bit of a hesitancy in terms of if it's not broken, don't try and fix it.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Sure.

Anthony Doyle
SVP and CFO, BioCryst

These patients remember when there were no treatments available to them, so there is a hesitancy in certain regards to switch. Some of it'll take time, additional evidence that we've been able to generate from a real-world perspective, but the switch market will continue to be important to us. And then on the acute side, again, there's no more well-positioned drug from a burden of treatment perspective than us in the market, where if you are taking acute only and you're having attacks, to move to a prophylactic treatment, and I think doctors, KOLs, et cetera, would advocate for patients to use prophylaxis for the treatment of HAE. So if you're gonna do it for the first time, then go into a once-a-day oral as opposed to an injectable. I think it's just the right play.

The market continues to go that way. It was 50/50, 60/40, it's probably 70/30 now in terms of prophylactic acute, treatments. There's about 7,500 patients diagnosed and treated here in the U.S., so there's still a lot of, room for us to grow in both of those regards.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Gotcha. Just going back to your comment in terms of, like, the discontinuation rate, it happens fairly early. Like you said, what's that kind of trended over the, you know, since the launch? Like, has it been pretty stable?

Anthony Doyle
SVP and CFO, BioCryst

Yeah.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Is it growing, shrinking, what?

Anthony Doyle
SVP and CFO, BioCryst

I think it has been stable, and if you kind of bifurcate it into those patients who are new to ORLADEYO, what we've said is that there's a 60% retention. So if 40% of patients are gonna discontinue within the first year, again, most of that's gonna happen in the first three months or so. We've been working on education and making sure that we can meaningfully move that down. About 50% of that is gonna be due to perceived lack of efficacy, and then the remainder due to other factors, including GI impact, and I think doctor and patient education, to make sure that they know what to expect when they're going into it, because if that's a surprise to you.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Yeah

Anthony Doyle
SVP and CFO, BioCryst

I t's a really bad surprise. And we've seen drop-offs where patients haven't kind of worked through some of those GI impacts. Others who have and have come out the other side, and usually they're mild and can be treated and worked through. We've also seen some boomerangs, where people have come back and kind of said, "Well, maybe I didn't give it a fair try because I've talked to somebody else who same thing happened, and then they did work through it. So I want to see if I can get onto the other side of that." So that's the kind of first year, and then if you get through the first year, the retention rate skyrockets.

As long as you can be well-controlled on our drug, patients are having a great experience, and I think it's life-changing to patients who've been seeing the medication in their fridge and had some issues with travel, and when do I go, and how do I take it, et cetera. So the freedom that a once-a-day oral brings, I think really well received, and I'm hopeful that we'll continue to see strong growth into the future.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Gotcha. I guess, from the learnings of the last, you know, couple of years since launch, in terms of that mitigation strategy, maybe around the GI or this perceived lack of efficacy, I mean, are you kind of arming docs with, you know, certain education things? Like, what are you doing to do that.

Anthony Doyle
SVP and CFO, BioCryst

Yeah

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

T o lower that rate? And then also, you know, is it just that some of these patients are, tend to be, like, late responders? Like, would they eventually, like, actually start to see efficacy, you know, beyond three months if they actually start, if they stay on the drug?

Anthony Doyle
SVP and CFO, BioCryst

Yeah, I think the education first and foremost as to what to expect.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Mm-hmm.

Anthony Doyle
SVP and CFO, BioCryst

Again, if these things come as a surprise, I think we've had some patients not know if actually they were just having GI side effects or if they were actually having an attack, a gastro attack. And so making sure that people are eyes wide open as to what they're going into has been most important, and then explaining how they can be treated, how long those GI effects might persist, and highlighting patients that have worked through and come out that other side. I think in terms of the not giving up too early, that's been some of the primary education that we've needed to do.

In terms of patients having a perceived lack of efficacy, you know, one of the biggest drivers for having HAE attacks is stress, and moving from one medication to another medication can be a stressful event. And so there are some things that we've talked about doing in terms of maybe it's a co-prophy type approach at the start.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Mm-hmm

Anthony Doyle
SVP and CFO, BioCryst

A nd then kind of leaning over into sole prophy on our drug. There are some things that we can do to try and mitigate that, but at the same time, you know, the drug is not gonna work for everybody.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Sure.

Anthony Doyle
SVP and CFO, BioCryst

None of the drugs in the space do. But for those who it does work for, it works really, really well. There's a really high efficacy rate from our long-term safety data. And so our approach is just to make sure that everybody out there gives the drug a try, everybody who wants to be treated with a once-a-day oral gives it a fair shot.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Gotcha. Like, how do you, like, you know, solve that anxiety from a patient? Like you said, like, that you make that switch. Again, is it kind of like that co-prophy, or are you putting it on top of, you know, other therapies?

Anthony Doyle
SVP and CFO, BioCryst

Yeah, we've tried a bunch of things.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

What, what are the type of things that physicians are doing to kind of, you know, mitigate that anxiety?

Anthony Doyle
SVP and CFO, BioCryst

Yeah, I think presentation of data in terms of what has worked previously and showing that the drug does work. Co-prophy can be a good strategy. I've learned from my personal life, telling people not to get stressed out, that generally doesn't work. So a lot of it is that real-world evidence and maybe getting them in contact with other patients who have gone through the same thing.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Yeah

Anthony Doyle
SVP and CFO, BioCryst

A nd have come out well on the other side, and what are some of the lessons learned? What have they seen? I think overall, just education and awareness, there can't be enough of it. And the more we arm patients and doctors alike with that, the better the outcomes that we've seen.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Got it. So maybe just talking about, you know, I guess the different geographic areas and kind of the opportunities you view for ORLADEYO, like.

Anthony Doyle
SVP and CFO, BioCryst

Yeah

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

A gain, U.S. and ex-U.S.

Anthony Doyle
SVP and CFO, BioCryst

Yeah. U.S. is the biggest opportunity.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Sure.

Anthony Doyle
SVP and CFO, BioCryst

And so for the billion-dollar peak, about 80% of it will come here in the U.S., and about a 27%, give or take, market share is what we need to get there, and we're on a strong path and trajectory to get there. Outside of the U.S., to date, the focus has been on Western Europe, so the U.K., France, Germany, Nordics, et cetera. Drug is already approved, and we've gone through the market access channels to get to a point where we're selling into those markets. We've also had approvals in places like Japan and Canada. Japan, we're licensing. Canada, we're doing it ourselves. And then other markets like Latin America, Middle East, Eastern Europe, we'll use distributor relationships.

Overall, what we expect is we'll be able to generate about $200 million in sales out of those markets at peak. You know, it'll probably be longer to get there based on there are markets that we're not even in yet that we need to get to peak in order to make those numbers. But overall, our expectation is to get ORLADEYO into all the countries where patients are looking to experience the drug and need that type of treatment. Europe will get there faster. It's a bigger market. It's a more experienced market and, you know, talking about the prophylactic versus acute-

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Mm-hmm.

Anthony Doyle
SVP and CFO, BioCryst

Europe is still, and other places are still behind in terms of acute medication, which is more prominently used. They're still using, there are still countries that are using androgens to treat the disease state, which I don't think should happen, and so we have an obligation to get into those countries. But more than anything for us, you know, I think they have the opportunity to meaningfully move the needle in the mid-term basis in terms of that revenue generation.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Like, in terms of payers, like, how much have they kind of shifted their thinking, prophy versus acute, in, in terms of coverage? And again, I think, you know, ORLADEYO has fairly good coverage, so maybe.

Anthony Doyle
SVP and CFO, BioCryst

Yeah

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

You can review that as well.

Anthony Doyle
SVP and CFO, BioCryst

Yeah, over 80%, and that doesn't mean there's not still work to be done. There is, whether it's individual insurers, PBMs, most of the big payers are on board. Individual plans, we might have to move the needle on. But if you look at health economics, when people are treating on an acute basis versus when they're using prophylactic, the benefit is there.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Mm-hmm.

Anthony Doyle
SVP and CFO, BioCryst

In terms of, reduced number of hospitalizations based on those attacks, you know, less fatalities, which is phenomenal for patients who are not can't get to rescue medications and might have a laryngeal attack on a timely basis. Internationally, there can be. Once you have your approval, depending on the country that you can you go into, there are different tactics to go in. An example is the U.K., where a competitor, Takhzyro, is approved for patients who have two attacks on a per-week basis and for reimbursement by the NHS, and we're approved for patients who have two attacks on a per-month basis. So the volume element in ex-U.S. is far more important.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Mm-hmm.

Anthony Doyle
SVP and CFO, BioCryst

Price can be a much bigger impact in terms of the discount factors, but still a big opportunity for us to get into those markets and to see volumes increase, but I think well covered.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Gotcha. Then just in terms of, like, your, you know, thoughts on the peak opportunity, and how does the pediatric, you know, kind of opportunity, is that part of that, or is that separate in terms of your, you know, kind of strategy there?

Anthony Doyle
SVP and CFO, BioCryst

It would be separate.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Okay.

Anthony Doyle
SVP and CFO, BioCryst

I, I think it has the benefit of being its own market. And so our product will be again, back to the idea of granules, it'll be almost sprinkles that go on to food.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Sure

Anthony Doyle
SVP and CFO, BioCryst

And kids can take. And so if it's that or an injectable, you know, we didn't rest on our laurels and say, "Have your kid try and swallow this pill.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Yeah.

Anthony Doyle
SVP and CFO, BioCryst

You know, kids are neither good at injectables nor pills. Being dynamic in terms of how we move that burden of treatment, I think, is going to be well received, and there's a market on a standalone basis for that. I'm hopeful that there's a familial, you know, halo effect that we might be able to get to, in terms of having multiple family members treated by the same drug. But that's not baked into the $1 billion. If we can get there, and I'm hopeful that we can, it'll be on top of that.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Gotcha. And then just overall, in terms of, like, what you're seeing and how the HAE market is kind of evolving, obviously, we've talked a lot about, you know, shift to oral, prophy versus acute. Like, what do we kind of think about in terms of the, you know, durability of the, the ORLADEYO franchise?

Anthony Doyle
SVP and CFO, BioCryst

Yeah. Again, it's a differentiated product in the market. Going after oral was a very defined strategy for the company. It's a hard target, and we ourselves had a failure in our first-generation drug for HAE. So we know, and have seen then from other competitors in the market, that it's a hard thing to do. I think in terms of durability, we're well placed, right? A lot of the new drugs that are coming in are either injectables, or they might be RNA, or they might be gene therapy. What our focus on is getting to as many patients as quick as we can, making sure that they are controlled on a once a day, such that when new competitors come into the space, what is the impetus for those patients to move to any other medication?

If it's to go to, you know, a burden of treatment where it's less frequent injectable, I believe that there's no burden of treatment that's less pervasive than having a once-a-day oral. So I think getting there as quickly as we can and then maintaining it, there's a strong place for us in the market, regardless of what happens, I think from a competitive perspective.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Got it. And then maybe just shifting over to the pipeline a little bit, just in terms of, you know, maybe just frame up what you guys are working on. And then I know from a complement perspective, there's been some fits and starts there, so maybe kind of just give us a little bit of the history there.

Anthony Doyle
SVP and CFO, BioCryst

Sure

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

And kind of how you guys have maybe learned from those experiences.

Anthony Doyle
SVP and CFO, BioCryst

Yeah. So BCX10013, we are moving forward in two avenues. One is, we've announced that we're gonna be recommencing SAD, MAD in additional cohorts just to get PK results in additional and increased doses. At the same time, we're gonna be moving forward with a PNH trial, where we're looking for, you know, probably around 15 patients worth of data. And what we're looking for is, do we have safety? Do we have efficacy and efficacy akin to both what is in the market and what we think will be in the market? And then do we have a once-a-day drug?

And if we do have a profile that if we have all of those things, will look like best-in-class, how do we move forward as quickly as we can in likely renal indications. PNH will use to get the biomarkers necessary to give us, you know, that AP inhibition, best-in-class profile. And if we don't, then we'll stop. Like, Our job is not to get to as quickly as we can on approval, it's to be competitive also within that space. And so first or best, and we're not gonna be first, so we're looking for a best-in-class profile. Probably next year is when we'll know if we have that.

If we do, we'll move forward as quickly as we can, and if we don't, then, you know, we feel like what we'll announce in November in terms of the pipeline that is behind that is worth the investment, and that's where we'll focus capital allocation.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

I guess just in the history of, like, kind of targeting Factor D, I mean, it's definitely, I mean, in just, I guess, targeting complement in general has been fairly tough. You know, we've seen some successes, but I guess, is there anything in terms of, like, how you view this molecule relative to the, the previous molecule and kind of the differences in terms of.

Anthony Doyle
SVP and CFO, BioCryst

Sure.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

You know, making sure that maybe, again, you're gonna be kind of closer to a best-in-class-.

Anthony Doyle
SVP and CFO, BioCryst

Yep.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Ish type of profile?

Anthony Doyle
SVP and CFO, BioCryst

Yeah. So we've learned lessons from prior failures, and when we pulled BCX9930, we did so because at that point in time, from a competitive perspective, we didn't think it was gonna be either of those two things. You know, we had some safety challenges with BCX9930 around increases in serum creatinine due to crystallization, and so we've done work with BCX10013. While it's, you know, same backbone.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Yeah

Anthony Doyle
SVP and CFO, BioCryst

I t's a different, unique molecule. And so as much as we have been able to do to make sure that we don't have those same issues in BCX10013, you know, still an early-phase molecule, but the work that we've done in the preclinical side and, you know, repeating some of the bench work that showed that crystallization, it's different.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Mm-hmm.

Anthony Doyle
SVP and CFO, BioCryst

We don't have those same issues. It's once a day, whereas BCX9930 was gonna be a twice-a-day drug. So if we have this competitive profile that we think we can get to, then we will move just as quickly as we can. But at the same time, if we don't have that, we're gonna be very disciplined in terms of that capital allocation, and we will move forward with other assets.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Can you just share with us, like, preclinically, what you've seen with this molecule? And again, is there any, again, not necessarily, like, red flags, but seemingly, it's, it's pretty clean, and, and it's got the right profile?

Anthony Doyle
SVP and CFO, BioCryst

Yeah. We announced earlier this year that we had slowed down the development of the asset due to some preclinical findings that we had, and it was in some inconsistencies between when you're doing your preclinical talks, you're gonna do some short-term work, some midterm work, and some longer-term work. And so in the midterm work, the kind of 39-week data, we saw some things come up in the first 13 weeks that we hadn't seen come up in the 13-week ClinTox trial that we ran, and so took some time to make sure that we were understanding what we were seeing.

Since then, you know, we've gone back to regulators with that work, with the PK, PD, PD data that we saw on the SAD MAD data, and gotten to the point where we could move forward with in-patient trials to try and prove or disprove the hypothesis of best-in-class once-a-day oral. So enough, enough to slow us down, but enough now to move forward with regulators to get into patients. And ultimately, the in-human data is gonna trump anything-

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Sure

Anthony Doyle
SVP and CFO, BioCryst

T hat we have on the animal side, and so that's what we would use to move forward into pivotals.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

I guess, why, you know, choose the renal area, you know, in terms of, you know, targeting with factor D? And, you know, obviously, this is actually an area that's kind of heating up.

Anthony Doyle
SVP and CFO, BioCryst

Yeah

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

I n terms of development. But, you know, why, why do you guys feel good about, you know, pursuing that?

Anthony Doyle
SVP and CFO, BioCryst

Yeah. I think from a scientific validation perspective, in terms of AP, alternative pathway inhibition and how it translates from PNH and those biomarkers into renal. Renal, yes, there's, it's a competitive market, specifically IgAN.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Mm-hmm.

Anthony Doyle
SVP and CFO, BioCryst

But I think from a validation perspective, we've seen some early validation and then, you know, if Novartis gets good data, I think that will only enhance that validation further. But it's a good-sized market. There's a lot of opportunity for, you know, multiple areas or multiple ways that you can treat IgAN from a disease state. We think alternative pathway inhibition is one of those. And then knowing that if you can get there from an IgAN perspective, there's definitely economies of scale in terms of how to go into some of those other renal indications.

And the likelihood of the validation working in some of those other indications, not to mention, you know, the benefit that you would then get from a commercialization perspective in terms of calling on nephrologists and not needing kind of multiple large armies to go after those same diseases.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Gotcha.

Anthony Doyle
SVP and CFO, BioCryst

Yeah. So for a company like us, I think it makes total sense.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

I mean, how do you think about that competitive landscape? Not only just, you know, within renal and other, you know, mechanisms, but even with just other complement inhibitors, oral complement inhibitors. Like, you know, obviously, you have to hit that profile, but-

Anthony Doyle
SVP and CFO, BioCryst

Yeah.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

You know, what does that need to look like? You know, have you seen, you know, other kind of, like, competitor data, you know, from other oral complement inhibitors?

Anthony Doyle
SVP and CFO, BioCryst

Yeah. The first one for us is to get the data in PNH.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Yeah.

Anthony Doyle
SVP and CFO, BioCryst

And so from a complement inhibition perspective, if we can be as good or better than what is currently out there, including the Novartis molecule-

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Yes

Anthony Doyle
SVP and CFO, BioCryst

G iven that we'd be looking for a once-a-day profile, we think that's gonna translate well into competing in that space. Is it monotherapy within some of the renal indications? We'll see. I think IgAN, depending on the diagnosis of IgAN and what some of the underlying factors are, I think there's the opportunity to use multiple treatments to go after IgAN. And we've said, you know, from the get-go, as much as we'll go after the alternative pathway, there's other opportunities for us to go after the classical pathway, the lectin pathway, the terminal pathway. Eventually, I think the market's gonna self-combine. There might be opportunities for us to combine them ourselves.

But the opportunity on a standalone basis for us to go into IgAN and other renal indications, it gives us the opportunity to have, you know, potentially another ORLADEYO behind ORLADEYO itself. And, you know, there's not a huge amount of companies out there that have commercial-stage assets, let alone multiple commercial-stage assets, and that would be our goal.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Got it. And then maybe we could talk about the R&D Day a little bit.

Anthony Doyle
SVP and CFO, BioCryst

Sure.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

So obviously, you know, excited about that. I mean, you guys have really kind of focused on kind of your expertise in medicinal chemistry and small molecule development. Maybe, is that something that you're gonna showcase, you know, at the R&D Day, in terms of your expertise there in developing new molecules? So that's maybe question one.

Anthony Doyle
SVP and CFO, BioCryst

Sure.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Then the second, yeah, I mean, how should we think about, y ou know, is this gonna be kind of a reveal, you know, on, like, areas that you wanna go that you haven't been yet? Like, in terms of, like, 'cause you kind of focused on, like, almost I&I and kind of rare disease. Is this gonna bring you into a whole new therapeutic area, or is this going deeper in the areas that you already are, you know, kind of, you know, commercializing and, and developing drugs in?

Anthony Doyle
SVP and CFO, BioCryst

Sure. Yeah, no, our continued focus is gonna be on rare disease, right? We are a rare disease company. We see value in that, both in terms of the expertise that we have and the ability for a company like ours to be competitive on a longer-term basis in terms of trial enrollment, and then on a forward basis in commercializing the asset. What we will talk about during that are assets and molecules that we haven't yet discussed with the public, so it will be an unveiling of newer things. You know, if we have an update to provide in terms of any of the things that we're doing, you know, maybe, but that's not the intent.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Mm-hmm.

Anthony Doyle
SVP and CFO, BioCryst

Right? The intent is to talk about new molecules for the company and how they fit in a company like BioCryst. You know, how did we, h ow do we develop them? Why do we choose the targets that we go after? What are the indications that they can treat? And to make sense of that in terms of the overall investment then that we have for the Birmingham team. So yeah, the R&D Day will be down in Birmingham, Alabama.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

All right

Anthony Doyle
SVP and CFO, BioCryst

On a Friday afternoon. You know, we've gotten some questions around. It's during

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Football season

Anthony Doyle
SVP and CFO, BioCryst

A heavy earnings season, so, you know-

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

I was gonna say football season.

Anthony Doyle
SVP and CFO, BioCryst

Football. There's a football, so there's a football match the day after as well.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Mm-hmm.

Anthony Doyle
SVP and CFO, BioCryst

I think Alabama are playing LSU, so we'd be hopeful to bring some people to that. But I think being there-

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Mm-hmm

Anthony Doyle
SVP and CFO, BioCryst

A nd seeing the expertise that the team brings to, again, not only molecule indication, selection, but how the team is differentiated in terms of how they take, you know, not only the molecule, but then, the atoms and how they fit them into active sites and, you know, what's the secret sauce, right? What is it that differentiates us, and why we think that we can bring a high, probability of success into these indications. I think it'll surprise people. You know, I think we're excited to do it. We're impressed with the work that the team has done, and we're excited to share it with people.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Gotcha. Maybe two questions to follow up on that.

Anthony Doyle
SVP and CFO, BioCryst

Sure.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

One, in terms of, you know, funding these newer programs, I mean, is this something that, you know, generally you can kind of take from basically concept here, preclinical, potentially all the way through with, you know, kind of what you're generating from ORLADEYO and, and kind of existing cash? And then second, just in terms of, you know, is this going to be, it, it sounds like it, but, like, it, it sounds like this is gonna continue to be in your comfort zone, potentially of like, I mean, maybe complement or something related to that. Is, is that kind of like a fair assumption, at least?

Anthony Doyle
SVP and CFO, BioCryst

Yeah, for second question first—we'll do what we're good at.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Yeah.

Anthony Doyle
SVP and CFO, BioCryst

Right? We're not looking to throw spaghetti at a wall and see what sticks. We know what we're good at. We know where to focus. We are focused not only on the discovery side of the house, but again, can we develop it, and is there a market for it? And if it doesn't fit all of those three things, then it's not gonna, it's not gonna make it into that discovery effort. So yeah, you know, we've already talked about there's an opportunity that we're going into C2. Again, we've already talked about going after multiple other areas in that complement pathway. So that will be a focus for the company. What was your first question?

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

The funding strategy.

Anthony Doyle
SVP and CFO, BioCryst

The funding? Yeah.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Yeah.

Anthony Doyle
SVP and CFO, BioCryst

Yeah. The CFO should know that one. So given that they're earlier phase, the requirements that we have from a funding perspective to get into what are those next stage gating elements, how do you de-risk the asset? The earlier phase, so they're cheaper-

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Right.

Anthony Doyle
SVP and CFO, BioCryst

Cheaper than going through proof of concept or, you know, phase 3 pivotals, for example. So massively cognizant from an, a capital allocation perspective, that we're not gonna do more than we can. And it's our job from a success perspective, to only bring those assets forward if they continue to generate the potential for additional value. So if we get to the point where I think now they're fundable based on what we have, if we get to the point further down the line where we're to need more funds, knowing that we can go into multiple areas of our cap table and, and do multiple deals. You know, we haven't done an equity deal since the summer of 2020.

And since then, we've utilized, we've utilized debt, we've utilized royalty, we've utilized debt again with Pharmakon and refinanced our existing debt at the beginning of the Q2. I would never say never, but given you know, where the market is at the moment, it's really not a good time to do it. And the only reason we would need additional funds is if we thought we had the opportunity to somehow supercharge one of those assets.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Mm-hmm.

Anthony Doyle
SVP and CFO, BioCryst

And go faster into the development cycle than we could without it. And then there's BCX10013, which we'll get a definitive answer as to whether we're moving forward next year into pivotal. So company's in a really good spot from a capital perspective. North of $400 million on the balance sheet. We have the option to take down another $150 million through third quarter of next year. And again, we would do that if we thought doing that provided value to us and investors alike. Company's never been in a stronger spot from a financial perspective to make these investments.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Got it. And maybe last question. So in terms of the, you know, programs that you'll kind of unveil and the targets and things like that, do these have, you know, kind of tried and true regulatory paths? Or are you gonna be kind of like, you know, paving your own, your own way in terms, again, are these, like, kind of more novel indications or, or novel targets that, again, there's maybe not a well-trodden regulatory path? I'm just kinda curious, like, what level of risk do you guys.

Anthony Doyle
SVP and CFO, BioCryst

Yeah

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Kinda look to take with, you know, kind of the pipeline?

Anthony Doyle
SVP and CFO, BioCryst

Yeah, I think we'll balance it, right? We're looking for strong scientific validation that the areas that we're gonna go after are gonna work. We're also not trying to do something that's gonna put extra risk on the asset just to do something novel. If there's the opportunity to work with the regulators to accelerate these molecules in diseases where unmet need is high, then as long as regulators are good and we have a line of sight to get there, but we're not gonna roll the dice and, you know, take undue risk just to do something novel or try to chase our tail or catch up with another asset. Again, our focus is first in class or best in class or both.

As long as we have one of those two things, then we think we have a strong competitive dynamic to bring a drug forward. So that's gonna be the focus.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

All right. Cool.

Anthony Doyle
SVP and CFO, BioCryst

Yeah.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Well, we look forward to it and be down in Alabama.

Anthony Doyle
SVP and CFO, BioCryst

Perfect.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

All right.

Anthony Doyle
SVP and CFO, BioCryst

Have a nice.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Good. Yeah, thanks, Anthony. Good to see you. All right.

Anthony Doyle
SVP and CFO, BioCryst

Thank you, sir.

Derek Archila
Managing Director and Biotechnology Equity Research Analyst, Wells Fargo

Yeah, of course.

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