Slide 1: Fourth Quarter 2024 Results Call
Fourth Quarter 2024 Results Call Corporate Update & Financial Results February 24, 2025 CONFIDENTIAL & PROPRIETARY
Slide 2: Forward-looking statements
Forward-looking statements BioCryst’s presentation contains forward-looking statements, including, but not limited to, statements regarding future results and forward-looking financial information, company performance, achievements, future market share or size, and expectations regarding pipeline de
Slide 3: Agenda
AGENDA Jon Stonehouse Corporate update President and Chief Executive Officer Charlie Gayer ORLADEYO® update Chief Commercial Officer Dr. Helen Thackray Pipeline update Chief Research and Development Officer Anthony Doyle Financial update Chief Financial Officer Q&A 3
Slide 4: BioCryst: durable, profitable growth through the decade with pipeline optionality
BioCryst: durable, profitable growth through the decade with pipeline optionality Marketed Product growing to $1B peak annual sales Financially Clinical Pipeline Independent with near-term milestones with near-term path to profitability 4
Slide 5: 2024 highlights and 2025 outlook
2024 highlights and 2025 outlook • 2024 Results: $438M global ORLADEYO revenue (34% growth) and $451M total revenue COMMERCIAL • Over 1,200 US prescribers EXCELLENCE • Commercially available in over 30 countries CLINICAL • ORLADEYO pediatric program on track for NDA submission to FDA in 2025 PROGRES
Slide 6: Strong ORLADEYO growth to continue in 2025
Strong ORLADEYO growth to continue in 2025 ORLADEYO REVENUE QUARTERLY & QUARTERLY AVERAGE BY YEAR ($M) 160 140 120 100 80 60 40 20 0 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 2Q 3Q 3Q 4Q 4Q 2021 2022 2023 2024 20252025* Guidance Revenue ($M) 123 252 326 438 535-550 Growth ($M) +123 +129
Slide 7: ORLADEYO growth + focused capital allocation to drive sustained profitability
ORLADEYO growth + focused capital allocation to drive sustained profitability $1B peak 1,000 800 By 2027: >$300M Operating Profit1 600 >$600M Cash 400 200 0 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 ORLADEYO revenue Non-GAAP operating expense¹ 1. Not including stock-based compensat
Slide 8: Market research: Allergist/Immunologist prescribing has grown significantly
MARKET RESEARCH: Allergist/Immunologist prescribing has grown significantly while current prescribers still intend to prescribe more LIKELIHOOD TO PRESCRIBE ORLADEYO PRESCRIBING METRICS ORLADEYO TO MORE PATIENTS 100% 97% 100% 93% 90% 26% +23% +7% 86% 80% Change in Change in extreme 52% 59% 80% extre
Slide 9: Market research: Intent to prescribe more ORLADEYO remains consistent
MARKET RESEARCH: Intent to prescribe more ORLADEYO remains consistent, with prescriptions coming mostly from prophylactic switches ALLERGIST-IMMUNOLOGISTS (A/Is) PRESCRIBING – Q4 ‘24 SOURCE OF FUTURE NEW ORLADEYO PRESCRIPTIONS – Q4 ‘24 (n=60 unique A/Is managing 660 HAE patients) (n=60 unique A/Is m
Slide 10: Market research: Patients prefer oral route of administration
MARKET RESEARCH: Patients on injectable LTP consistently show strong preference for oral route of administration ROUTE OF ADMIN PREFERENCE AMONG CURRENT INJECTABLE PROPHY USERS Current Injectable Users (n=249) 100% 80% 48% 56% 60% 40% 33% 26% 20% 20% 18% 0% 2023 Survey 2024 Survey (n=120) (n=129) Pr
Slide 11: Comprehensive annual research + market simulation
Comprehensive annual research + market simulation OUR MODEL STARTS WITH PREFERENCE AND SIMULATES 6,000 MARKET INTERACTIONS BETWEEN HCPS, PATIENTS, & PAYERS Research Sample* Market Model Simulation (Monte Carlo) 11. A patient, physician, and payer are randomly selected from survey respondents. 2 The
Slide 12: Monte Carlo simulation outcome: U.S. prophy market share
Monte Carlo simulation outcome: U.S. prophy market share ORLADEYO REACHES A STEADY STATE OF OVER 2,000 PATIENTS IN U.S. DURING 2028, EVEN AS NEW PRODUCTS GAIN SHARE 100% 80% Prophylaxis Patient Share 60% 40% 20% 21% 22% 24% 25% 24% 24% 24% 23% 23% 20% 0% 2024 2025 2026 2027 2028 2029 2030 2031 2032
Slide 13: Our pipeline
Our pipeline ASSET PROGRAM LEAD PRE- PROOF OF PIVOTAL‡ APPROVED / OPTIMIZATION CLINICAL CONCEPT† COMMERCIAL ORLADEYO® (berotralstat) Hereditary Oral Plasma Kallikrein Angioedema Inhibitor (HAE) ORLADEYO® (berotralstat) Hereditary Oral Plasma Kallikrein Angioedema Inhibitor (age ≥2 years) (HAE) BCX17
Slide 14: This is BIG: bringing ORLADEYO to children
This is BIG: bringing ORLADEYO to children • Despite significant innovation in HAE prophylaxis for adults, there is still high unmet need in children • Injectable therapies are the only FDA-approved options for children ages 2 to 11 • Positions ORLADEYO to be the market leading prophylaxis for child
Slide 15: Treating Netherton syndrome with a targeted KLK5 inhibitor: BCX17725
Treating Netherton syndrome (NS) with a targeted KLK5 inhibitor: BCX17725 High Severe, rare, genetic and lifelong unmet disease with no approved targeted therapies need Well-understood biological cause: Validated mutation in SPINK5 gene target BCX17725 functionally replaces the missing protein Under
Slide 16: BCX17725 addresses the underlying disease biology in Netherton syndrome
BCX17725 addresses the underlying disease biology in Netherton syndrome • Patients with NS have a mutation in the SPINK5 gene NS SKIN which causes a deficiency in the SPINK5 protein HEALTHY SKIN neutrophils • The SPINK5 protein is an important natural regulator of KLK5, a serine protease involved in
Slide 17: Addressing DME with a potent plasma kallikrein inhibitor: avoralstat
Addressing DME with a potent plasma kallikrein inhibitor: avoralstat suprachoroidal injection1 Alternative Right drug Significant MOA + delivery market opportunity Compelling evidence for plasma High potency and low kallikrein activity in DME solubility/depot effect are attractive pathobiology ~1.5M
Slide 18: Avoralstat: a potent drug targeting DME
Avoralstat: a potent drug targeting DME Potential to treat all DME Patients via VEGF-independent pathway • Hyperglycemia damages retinal vasculature • Damaged endothelium activates plasma Kallikrein (pKal) • Elevated pKal levels seen in vitreous of DME patients • Elevated pKal produces bradykinin le
Slide 19: Preclinical evidence demonstrates plasma kallikrein pathway may reduce vascular leakage
Preclinical evidence demonstrates plasma kallikrein pathway may reduce vascular leakage Pre-Dosing Avoralstat (7 Days post dose) Pre-Dosing Avoralstat (6 Days post dose) Vascular leakage Vascular leakage Vascular Stability Vascular stability Source: BioCryst Pharmaceuticals nonclinical data on file
Slide 20: Suprachoroidal injection leads to 3+ months of sustained avoralstat levels
Suprachoroidal injection leads to 3+ months of sustained avoralstat levels in the retina1 1. BioCryst Pharmaceuticals nonclinical data on file 2025 This slide shows preclinical results, and the outcome of preclinical testing and early clinical trials may not be predictive of the success of later cli
Slide 21: Financial independence and clear path to profitability
Financial independence and clear path to profitability 2024 2025 2026 Full year Approach quarterly Full year operating profit1 positive EPS & cash- positive EPS & flow in 2H cash-flow 1. Not including stock-based compensation 21
Slide 22: Key milestones in 2025
Key milestones in 2025 2025 File pediatric NDA for ORLADEYO 2025 Begin avoralstat clinical evaluation in patients 2H25 Obtain initial BCX17725 clinical data 2H25 Approach sustainable quarterly positive EPS & cash flow 22
Slide 23: Finance summary
Finance summary (Figures in millions) Q4 2024 CASH POSITION Cash, cash equivalents, restricted cash & investments at December 31, 2023 $391 Cash, cash equivalents, restricted cash & investments at December 31, 2024 $343 Senior credit facility1 $324 2025 FY GUIDANCE Prior Current ORLADEYO revenue $51
Slide 24: Traditional debt and royalty breakdown
Traditional debt and royalty breakdown December 31, 2024 2023 Royalty financing obligations - current 32,676 23,565 Royalty financing obligations - long-term 481,053 508,034 Total royalty financing obligations 513,729 531,599 Secured term loan 314,869 303,231 Traditional Debt Commercial Royalty Init
Slide 25: Royalty obligations: terms
Royalty obligations: terms Rate Tiers Rate Tiers Cumulative Upfront Product (Key Territories2) (Other Markets2) Payback Cap $0-350M: 8.75% $0-150M: 20% RP $125M ORLADEYO $350M-550M: 2.75% $150M-230M: 10% None 2020 Over $550M: None Over $230M: None $0-350M: 0.75% $0-150M: 3% RP $150M 1 ORLADEYO $350M
Slide 26: Fourth Quarter 2024 Results Call
Fourth Quarter 2024 Results Call Corporate Update & Financial Results February 24, 2025 CONFIDENTIAL & PROPRIETARY