$0.85
$7.94
bear $0.85
base $3.72
bull $7.94
margin of safety $1.75
market price* $7.79
BioCryst is, for practical purposes, a one-product company. ORLADEYO (berotralstat) is a once-daily pill that prevents attacks of hereditary angioedema (HAE), a rare genetic swelling disorder. It produced about $549 million of United States sales in 2025 and $306.5 million in the first half of 2026, and the company expects $625 to $645 million for 2026. The European business was sold to Neopharmed Gentili on October 1, 2025 for $254.5 million. That sale is the main reason 2025 shows the company's first profit: of 2025's $250.8 million of owner earnings (cash from operations after removing working-capital swings, stock compensation and upkeep capital spending), about $243 million came from the sale. Without it the business roughly broke even. In every year from 2016 to 2024 it consumed cash, between $0.52 and $1.06 per share a year. Because the past ten years describe a drug developer becoming a commercial company, no historical average describes the business today. We start instead from the run rate the filings now show. In the second quarter of 2026, ORLADEYO sales grew about 10% from a year earlier on a like-for-like basis, the company was profitable, and it expects operating costs of $420 to $440 million for 2026, excluding stock pay and one-off deal costs. The last completed year's owner-earnings growth is not a usable number, since the business went from losses to a one-off gain. Our base case's first year, 2027, assumes ORLADEYO sales of about $645 million, roughly flat on the 2026 guided midpoint and well below the recent 10% pace. Three groups of creditors stand ahead of shareholders. First, a $400 million Blackstone term loan, drawn in January 2026 to help pay for Astria Therapeutics, carries floating interest of three-month SOFR plus 4.50% (with a 1.75% floor), is secured on substantially all assets and is due in a single payment on January 23, 2031. Second, the company has sold three streams of ORLADEYO royalties, to RPI in 2020 and 2021 and to OMERS in 2021. On the first $350 million of annual direct sales these take 19.5% off the top, and on sales between $350 and $550 million they take 7.5%. Carried at $426.8 million on June 30, 2026, they absorbed $85.7 million of royalties in 2025. The OMERS stream ends once OMERS has received $232.5 million; the two RPI streams have no cap. Third, Astria cost $637 million of cash plus stock and was mostly written off as $697.8 million of purchased research. Shareholders' equity is negative $454 million. Against that, the company held $352.6 million of cash and investments at June 30, 2026. How we valued it: we estimate the cash the business produces before paying lenders and royalty holders, discount it, and then deduct what is owed. We count the royalty streams at the present value of the payments they will actually take on each case's sales path, not at their book value. We deduct the term loan in full, plus about $35 million for the extra cost of its interest rate over the remaining four years, and add back about $300 million of cash beyond what the business needs to operate, a net deduction of about $135 million. Taxes are kept very low through 2032 because of past losses carried forward, and at 21% after that. Competition is the central risk. HAE patients can now choose among Takeda's TAKHZYRO injection, CSL's ANDEMBRY and Ionis's DAWNZERA, KalVista's EKTERLY on-demand pill, and a pipeline that includes Pharvaris's oral deucrictibant, which has reported successful late-stage results, and Intellia's one-time gene-editing treatment lonvo-z, which the FDA accepted for priority review in September 2026. ORLADEYO's appeal is that it is the only once-a-day oral preventive. That advantage narrows if an oral rival is approved, and a one-time cure would shrink the pool of patients needing chronic therapy. On patents, six ORLADEYO Orange Book patents run to 2035 and are not challenged. Annora Pharma has challenged four later patents that run to 2039, and BioCryst sued in March 2025. Base case ($3.72 per share): ORLADEYO holds about $645 million in 2027, then erodes slowly to about $550 million by 2034 as oral and gene-editing competitors take new patients. Generics arrive when the unchallenged patents expire in 2035, and sales collapse within two years. Research spending falls from about $175 million in 2027, when the navenibart late-stage trial completes, to about $80 million. The business is worth about $1.55 billion. Royalty holders take about $433 million of that and the loan net of surplus cash about $135 million, leaving roughly $985 million for shareholders. Bear case ($0.85 per share): an approved oral preventive, together with gene editing, repeats what happened to older HAE drugs when better options arrived: Shire's Cinryze infusions lost much of their preventive use within a few years of TAKHZYRO's 2018 launch. ORLADEYO falls from about $620 million in 2027 to about $320 million by 2030. Costs are cut but not as fast as sales, and generics still arrive in 2035. The business is worth about $705 million, royalty holders take about $345 million, and after the loan net of cash about $225 million is left for shareholders. After interest and royalties, cash in this case only edges up from today's roughly $350 million to roughly $500 million by the end of 2030. That is enough to repay the $400 million loan due in January 2031, but it would leave only about $100 million in a shrinking business, so in practice the company would probably refinance on worse terms. The business still carries its interest bill in every year, which is why the case keeps a small positive value. Bull case ($7.94 per share): demand, price increases and the label extension to children aged 2 to 11 carry ORLADEYO to about $750 million by 2029. Sales then hold near that level, the 2039 patents are upheld against Annora, and exclusivity runs to 2039. The business is worth about $2.76 billion, with royalty holders taking about $523 million. What we left out: navenibart, Astria's injection given every three or six months, finished enrolling its pivotal trial in June 2026, with results expected in the third quarter of 2027. Because it is not approved, no case includes any navenibart sales. All three cases do bear its trial costs, and the base case includes the European licence payments already contracted with Neopharmed. Approval would add value that none of these figures contains. Early-stage programmes such as avoralstat and BCX17725 are also excluded. Margin of safety price ($1.75): we are reasonably confident about ORLADEYO's next two years, because sales are growing and guided, and much less confident about anything after 2028. One product supplies almost all the profit. The worst plausible outcome is an oral rival plus a one-time cure taking patients faster than our bear case assumes, at the same moment the $400 million loan falls due in 2031. The secured lender and the uncapped royalty holders would then come first, and shareholders could face heavy dilution. The two things we are most likely to be wrong about are how fast competitors take share and whether the 2039 patents hold. Get both wrong on the downside and the shares are worth well under $1. The company pays no dividend, so any return has to come from cash building up and value being recognised over two to four years. At $1.75, the equity would be priced at about $465 million. Even in the bear case, the business generates roughly $120 million of cash for shareholders, after interest and royalties, over 2027 to 2029, on top of the cash already on hand. In the base case it generates about $335 million over the same three years, roughly 70% of that price. That is enough cash return to justify a 20% annual target despite the single-product risk, and a navenibart approval would be upside we have not counted. Above roughly $2, a few years of competitive erosion would erase the margin. Our previous estimate was built on a different basis, so its figures are not comparable with these. The main change in the business since then is that Intellia's one-time gene-editing treatment moved closer to market when the FDA granted it priority review in September 2026.