BioCryst Pharmaceuticals, Inc. Q3 FY2025 earnings call

• ORLADEYO continues to show strong revenue growth despite new competition, with a growing prescriber base. - The sale of the European business has cleaned up the balance sheet and put the company in a strong financial position. - Progress with pipeline includes early data expected from the DME program early next year, with plans to spin out or partner if outside rare disease focus. - BCX17725 Phase I study shows encouraging data on safety, systemic exposure, and distribution to the epidermis. - Announcement of the proposed acquisition of Astria, expected to close in Q1 2026, adding navenibart to the pipeline. - Ron Dullinger to succeed Charlie Gayer as Chief Commercial Officer on January 1.

ORLADEYO generated total revenue of $159.1 million, representing 37% year-over-year growth. Of this, $141.6 million (89%) came from the U.S. This strong performance is on a growing revenue base, well on its way to $1 billion at peak.

• Raised ORLADEYO revenue guidance to between $590 million and $600 million for the year. - Lowered non-GAAP OpEx guidance to $430 million to $440 million from $440 million to $450 million. - Anticipates staying profitable on a non-GAAP basis and cash flow positive even during navenibart development. - Expects navenibart to drive double-digit HAE revenue growth into the 2030s after ORLADEYO reaches a steady plateau.

• Potential impact of new competition on ORLADEYO's market share. - Regulatory risks associated with pipeline programs, such as Netherton syndrome trial enrollment and approval. - Uncertainties related to the spin-out or partnership of the DME program if initial data is not as expected.

Q: Of the 37% year-over-year ORLADEYO net revenue growth, how much of that was volume? And how much of that was better paid rate or net price? And on that front, how should we think about gross to net this quarter and going into 2026? And very quickly, how confident are you that you can maintain steady patient retention rates given the increasingly competitive landscape?

A: Of the 37% growth, a significant portion was price based on improvement in paid rate, particularly in the Medicare segment. Volume is growing as expected. Patient retention has been unchanged and is not affected by new competition. Gross to net is still about 15% and expected to be in 15% to 20% next year.

Q: One question with respect to the new prescriber numbers. I think this is the second quarter in a row you've been over 60. Just curious if you have any feedback, market research that can help us understand why they're deciding to prescribe now? What has been kind of the motivating factor more recently to accelerate the adds here? And then I guess, if you could share a little bit more color on what would the expected blended royalty rate look like in '26? I know you're projecting a step down over time here, but just kind of curious how we should be thinking about it directionally from '25 to '26.

A: Motivating factors include physicians becoming more comfortable with ORLADEYO's long-term and real-world evidence of effectiveness. We target prescribers accurately, including those with smaller patient bases. The blended royalty rate continues to decline, with the rate in the early teens and expected to go into single-digits over time.

Q: Congrats on the progress. So we have a couple of questions. First, on the new entrants, our KOLs do indicate there are a couple of patients switching from ORLADEYO to injectables, but the same clinicians are also saying that they expect ORLADEYO's share to stay stable. So beyond this anecdotal feedback and obviously, you all have highlighted the 1-year 60% retention. Are you able to share any recent metrics to suggest ORLADEYO is unlikely to be impacted by these injectable entrants? That's the first question. And then the second is on that pediatric HAE approval. As we approach the PDUFA date, maybe help us understand your views on the opportunity and what commercial strategy and preparation is ongoing to really make sure you all maximize that pediatric expansion? Are many of these patients already identified? Just help us understand as we get to the new year, any type of expectations around maybe some latent patient demand.

A: Market research and conjoint analysis show ORLADEYO remains sticky with no change in retention rates. For pediatric approval, there are about 500 HAE patients under age 12, with only 40% on prophylaxis. The commercial team is ready to launch post-approval, targeting physicians treating pediatric HAE.

Q: I was hoping you could expand on the decision to deemphasize, I guess, avoralstat for DME. Have you had an early look at the Phase I data there? And then looking at the updated pipeline slide, the undisclosed programs listed for rare diseases, at least that are preclinical. Can you give us some insights into what you're working on there preclinically and how close it might be to the clinic?

A: No early data on avoralstat yet; decision based on focus and expense to fund navenibart. Undisclosed preclinical programs are early and exciting, but details will be shared when ready.

Q: Congrats on the progress. I'll just ask a couple of quick ones on Netherton. Wondering if you could just talk more about the slower enrollment there and how many patients you'll have in the first quarter data update next year? And do you anticipate dosing higher than the 12 mg per kg? And I'm wondering if you're still exploring the subcu dose? Or is it going to be an IV dosing going forward?

A: Slight delay in enrollment, but enthusiasm is high from healthy volunteer data. Exploring both subcutaneous and IV dosing, and may explore higher doses. First quarter data expected from Part 3 of the trial with a few Netherton patients.

Q: Congrats on the continued progress in the quarter. Maybe just continuing on Netherton. Can you elaborate a little bit more on, I guess, what you're seeing from a PK/PD standpoint in those first couple of parts of the ongoing study? And I'm also curious what the trigger was for starting that Part 4, which I know you started in recent weeks. And then just secondarily, separately on ORLADEYO, just wondering what you're seeing in terms of demand from the normal C1 inhibitor population. I think that was a growth driver you cited in the past.

A: Netherton is a disease with no plasma/serum biomarkers, and there could be a disconnect between plasma concentration and epidermal effects. Part 4 enables longer-term dosing. On ORLADEYO, about 1/3 of patients are C1 normal, consistent with past trends.

Q: Just looking at sales so far this year in your guidance, it's implying that we're going to see a drop in quarter-over-quarter sales for the first time. We haven't seen that seasonality before. So hoping you could talk a little bit about your expectations, what's driving that? And if that's something we should expect moving forward or if this is going to be a one-time seasonality effect?

A: The drop is a one-time seasonality due to the sale of the European business, which was contributing $10 million to $15 million in revenue. Next year, there will be no such drop.

Q: Just wanted to touch on pediatric ORLADEYO with the ongoing review and the PDUFA in mid-December. Just curious if you guys have seen any impacts from the government shutdown, whether you've had continuous feedback from the FDA and whether you expect them to still meet that PDUFA. And then pending product availability, do you have any expectations for how the payer landscape will look in this segment? And whether or not you could expect a bolus of patients to come on board early upon product launch?

A: Interactions with FDA are ongoing with no concerns from the government shutdown. Payer landscape is favorable, and a bolus of patients is expected upon launch, but details will be updated post-launch.

Q: Wanted to ask about the Netherton syndrome also regarding the 12-milligram per kg IV dosing, by the way, very impressive biomarker data. I'm wondering what kind of safety you see in the patient -- in the healthy volunteer data? And then also, regarding the first quarter, the Part 3 data. So maybe if you can lay out what we should expect from this 1Q '26 data update from Part 3? And quickly, just housekeeping questions regarding ORLADEYO. I know you mentioned some of the comments, but I do wanted to double check with the actual numbers regarding the retention rate, are we still similar around 60% and the pay rate, I think last quarter, we talked about could be by year-end, 82% to 83%. Is that still the same? And then lastly is the patient segment, 50% switch from other prophy, is that still the same?

A: Healthy volunteer data shows the drug is very safe and well tolerated. Part 3 data from first quarter will provide insights on short-term effects in Netherton patients. ORLADEYO retention rate remains around 60%, pay rate ended Q3 at 82% and expected to adjust in Q4, with about 50% of patients switching from other prophy.