Pharming Group Nv · EURONEXT:PHARM
Pharming Group Nv — 37th Annual Roth Conference 2025
48 slides from Pharming Group Nv's conference presentation, March 2025
Slide 1: Pharming Group N.V. 37th Annual Roth Conference
Pharming Group N.V. 37th Annual Roth Conference March 16 - 18, 2025 NASDAQ: PHAR | EURONEXT Amsterdam: PHARM
Slide 2: Forward-looking statements
Forward-looking statements This presentation may contain forward-looking statements. Forward-looking statements are statements of future expectations that are based on management’s current expectations and assumptions and involve known and unknown risks and uncertainties that could cause actual resu
Slide 3: Building a leading global rare disease biopharma company
Building a leading global rare disease biopharma company Strong performance reinforces growth foundation Revenues: FY24: US$297 million (+21%) 4Q24: US$93 million (+14%) EURONEXT AMS: PHARM Nasdaq: PHAR Operating profit and positive operating cash flow in 3Q-4Q 2024 Growing commercial RUCONEST® for
Slide 4: Growing commercial portfolio
Growing commercial portfolio RUCONEST® Joenja® Strong U.S. in-market demand Increasing APDS patients on therapy U.S. physician prescriber base +11% in FY24 Found >240 in the U.S. and >880 globally New enrollments up 24% in FY24 Paid therapy: 96 patients + 5 pending (U.S.) Additional 188 patients on
Slide 5: Expanding rare disease pipeline
Expanding rare disease pipeline 5
Slide 6: RUCONEST for HAE
% Pharming’ RUCONEST® for HAE
Slide 7: RUCONEST: 2nd most prescribed therapy for acute HAE attacks in the US
RUCONEST® (rhC1INH): 2nd most prescribed therapy for acute HAE attacks in the US Only recombinant treatment that targets the root cause of HAE by replacing C1-INH Only recombinant treatment that acts at multiple points in the cascades leading to HAE attacks 97% patients needed just 1 dose1 93% acute
Slide 8: RUCONEST addresses patient needs unmet by other therapies
RUCONEST® addresses patient needs unmet by other therapies Type 1, Type 2, and Normal C1-INH HAE patients rely on RUCONEST RUCONEST patients experience moderate to severe Time of taking 24 hours after 4 hours after attacks, and attack more frequently RUCONEST RUCONEST patients switching from other a
Slide 9: Joenja (leniolisib) for PIDs
Joenja® (leniolisib) for PIDs
Slide 10: APDS is a rare primary immunodeficiency (PID)
APDS is a rare primary immunodeficiency (PID) Genetic defect leads to PI3Kδ hyperactivity Hyperactive PI3Kδ results in dysregulated Immune imbalance leads to diverse signs B and T cell development1-3 and symptoms1,4-6 Severe, recurrent, persistent infections The PI3Kδ enzyme • Sinopulmonary p110δ •
Slide 11: Joenja: first and only approved therapy for APDS
Joenja®: first and only approved therapy for APDS, corrects the underlying immune defect Joenja® (leniolisib) is a prescription FDA approval (March 2023) based on medicine that is used to treat randomized pivotal study and OLE study activated phosphoinositide 3-kinase U.S. launch (April 2023) delta
Slide 12: Reaching more APDS patients and expanding the addressable patient population
Joenja® (leniolisib) – Reaching more APDS patients and expanding the addressable patient population Potential total prevalence ~40 patients / million Genetic PIDs prevalence +7.5 patients / million APDS prevalence ~1.5 patients / million Joenja for CVID Joenja for PIDs with immune VUS resolution wit
Slide 13: Finding more APDS patients - VUS focus
Finding more APDS patients - VUS focus Variants of Uncertain VUS study results Significance VUSs: insufficient data to High throughput screening (MAVE) determine if variant is disease study, completed in December, causing identified novel variants leading to PI3Kδ hyperactivity >1200 patients in the
Slide 14: Pediatric APDS clinical trial results support regulatory filings
Pediatric APDS clinical trial results support regulatory filings Pediatric Phase III trial for children 4-11 years old with APDS Positive topline data announced December 2024 21 patients enrolled in U.S., Europe, and Japan Both co-primary endpoints show improvement consistent with the RCT in adolesc
Slide 15: Leniolisib for PIDs with immune dysregulation beyond APDS
Leniolisib for PIDs with immune dysregulation beyond APDS PI3Kδ activity drives immune dysregulation in PIDs, providing strong rationale for development of leniolisib All PIDs PIDs with immune dysregulation linked to PI3Kδ signaling PIDs with immune dysregulation • Multiple genetically identifiable
Slide 16: Joenja development status
Joenja® (leniolisib) development status Expanding the addressable patient population Geographic expansion Pediatric expansion Indication expansion (APDS) (APDS) (additional PIDs) Europe – review extended to Jan. 2026 PIDs with immune dysregulation 4 to 11 years – Positive topline data Single outstan
Slide 17: KL1333 for mtDNA Mitochondrial Disease
KL1333 for mtDNA Mitochondrial Disease
Slide 18: KL1333 for mtDNA mitochondrial disease (Abliva acquisition)
KL1333 for mtDNA mitochondrial disease (Abliva acquisition) Primary mitochondrial diseases – rare disorders impairing mitochondrial energy production • Severe fatigue, myopathy (muscle weakness), and reduced life expectancy • Poor quality of life (e.g., loss of job, social isolation, depression) KL1
Slide 19: FALCON study – positive interim analysis
FALCON study – positive interim analysis Pivotal FALCON Study Interim Futility Analysis: Positive outcome achieved, with both primary endpoints having WAVE 1 – Fully enrolled passed futility 40 patients recruited across six countries (U.S., UK, France, Spain, Belgium, Denmark) Promising differences
Slide 20: Financials and Outlook
% Pharming’ Financials and Outlook
Slide 21: Financial highlights: 4Q 2024 vs 4Q 2023
Financial highlights: 4Q 2024 vs 4Q 2023 Revenues Gross profit OpEx development RUCONEST Joenja R&D G&A M&S Amounts in US$ million Amounts in US$ million Amounts in US$ million 80.5 92.7 74.1 81.2 13.1 73.6 73.9* 7.9 27.0 37.9 73.3 79.6 24.6 24.1 22.3 11.6 4Q 2023 4Q 2024 4Q 2023 4Q 2024 4Q 2023 4Q
Slide 22: Financial highlights: FY 2024 vs FY 2023
Financial highlights: FY 2024 vs FY 2023 Revenues Gross profit OpEx development RUCONEST Joenja R&D G&A M&S Amounts in US$ million Amounts in US$ million Amounts in US$ million 261.8 297.2 220.1 272.6 245.3 45.0 248.8 18.2 118.8 124.0 227.1 252.2 70.6 55.9 68.9 83.2 FY 2023 FY 2024 FY 2023 FY 2024
Slide 23: Abliva acquisition completed
Abliva acquisition completed Acquisition Terms Financial Details Timing Acquisition through a public Acquisition of shares with Announced ownership exceeding tender offer under Swedish available cash 90% on February 20 and initiated Takeover Act and Nasdaq delisting activities KL1333 in-licensed by
Slide 24: 2025 Financial guidance
2025 Financial guidance Revenue and operating expenses: FY 2025 Guidance Notes Total Revenues US$315 - 335 million 6 - 13% growth Operating Expenses Flat vs. FY 2024 (pre-Abliva impact) Operating Expenses Preliminary estimate including R&D and non- ~US$30 million (Abliva-related) recurring transacti
Slide 25: Building a leading global rare disease biopharma company
Building a leading global rare disease biopharma company Growing commercial RUCONEST for acute HAE attacks portfolio Joenja (leniolisib) for APDS – U.S. and EU/Rest of World Additional patient finding Reaching more APDS Targeted geographic expansion patients with Joenja Pediatrics label expansion Pi
Slide 26: www.pharming.com
www.pharming.com NASDAQ: PHAR | EURONEXT Amsterdam: PHARM
Slide 27: Appendix
Pharming Group N.V. Appendix
Slide 28: APDS can impact many facets of life
APDS can impact many facets of life Physical1,2 Frequent infections Social3,4 Swollen glands Missing school, work, or Shortness of breath daily activities Coughing/wheezing Chest or joint pain Fatigue Treatment Burden1-4 Inability to exercise Frequent hospitalizations Hearing loss Surgeries Diarrhea
Slide 29: Heterogeneous, evolving symptomology can often lead to missed diagnoses
Heterogeneous, evolving symptomology can often lead to missed diagnoses Timeline of the most common pathologies* seen in APDS1-4 Median age at diagnosis: 12 years (7-year median diagnosis delay) <1 year 3 years 5 years 10.5 years 11.2 years† 18 years (range, 1 month-10 years) (range, 1-6 years) (ran
Slide 30: Management for APDS prior to Joenja
Management for APDS1,2 prior to Joenja® Immune Deficiency Immune Dysregulation • Antimicrobial prophylaxis • Corticosteroids • Immunoglobulin • Other immunosuppressants replacement therapy • mTOR inhibitors None of these therapies are FDA- approved for APDS treatment Hematopoietic stem cell transpla
Slide 31: Joenja clinical trial designs
Joenja® clinical trial designs Pivotal Trial - Pivotal Trial - Part 2: Open-label Part 1: Efficacy extension Dose- & Safety study4,5 finding1,2 Evaluation3 Nonrandomized, open-label, Randomized, triple-blinded, Nonrandomized, open-label, dose-escalating placebo-controlled long-term study 31 patients
Slide 32: Joenja addresses the underlying cause of APDS – Phase 3 co-primary endpoints
Joenja® addresses the underlying cause of APDS to help restore immune balance – Phase 3 co-primary endpoints At 12 weeks Joenja® decreased lymphadenopathy and increased naïve B cells Change from baseline in index nodes* Change from baseline in naïve B cells† Log10-transformed SPD of index lesions Jo
Slide 33: Joenja significantly reduced splenomegaly
Joenja® significantly reduced splenomegaly Secondary endpoint: Significant reductions in at week 12 spleen size by 2D and 3D analysis compared to placebo 27% reduction in 3D spleen volume* • The adjusted mean difference in bidimensional spleen size between Joenja® (n=19) and placebo (n=9) was -13.5
Slide 34: Joenja reduced IgM levels
An exploratory endpoint showed Joenja® reduced IgM levels Mean serum IgM rapidly reduced to within normal limits • In the Joenja® arm, IgM was 600 elevated above normal limits in 6 patients at baseline, and by week 12 was reduced in all, with 50% returning to IgM, mg/dL 400 within normal limits • In
Slide 35: Joenja safety profile
Joenja® safety profile Phase 3 Trial1,2 Open-label Extension Study3 Data cutoff for interim analysis: December 13, 2021 Adverse reactions reported by ≥2 patients treated with Joenja and more frequently than placebo Joenja (n=21) Placebo (n=10) • 32/37 patients Most common AEs n n (%) n (%) reported
Slide 36: Open-label extension interim analysis of infections and IRT reduction
Open-label extension interim analysis of days spent with infections and IRT reduction Annual Rate of Infection Days* Physician-reported IRT Reduction‡ 45 40 42.4 Of 27 patients receiving IRT: Days with infection per patient (m/N) Baseline† Baseline† 35 39.0 38.5 30 25 Baseline† 26.7 20 Baseline† 22.
Slide 37: VUS by the numbers
VUS by the numbers VUSs frustrate patients and doctors, limiting diagnosis of genetic diseases such as APDS Pharming is aware of ~1,200 US patients harboring PIK3CD/R1 VUSs • This figure will continue to grow over time • VUS are identified at ~4x the rate of likely pathogenic/pathogenic (LP/P) varia
Slide 38: PI3Kδ signaling alterations drive immune dysregulation in PIDs
Given importance of PI3Kδ in B & T cells, immune dysregulation in PIDs can occur via alterations in PI3Kδ signaling Altered PI3Kδ signaling can occur in multiple Clinical manifestations, disease onset PID genetic disorders beyond APDS and severity similar to APDS 5-10 (ex: ALPS-FAS, CTLA4, NFKB1, PT
Slide 39: PIDs linked to PI3Kδ signaling – Phase II study design
PIDs linked to PI3Kδ signaling – Phase II study design Phase II proof of concept clinical trial – single arm, open- label, dose range-finding study (N=12) 10mg 30mg 70mg • Patients with PIDs linked to PI3Kδ signaling, e.g. Lead Investigator: Gulbu Uzel, M.D., Senior ALPS-FAS1, CTLA4 haploinsufficien
Slide 40: Dysfunctional mitochondria produce less ATP
Dysfunctional mitochondria produce less ATP Primary Mitochondrial Disease (PMD) Mitochondria, often described as the “powerhouses” Dysfunctional Mitochondria of cells, are crucial for energy production Mutation Impaired ETC protein expression Mitochondrial diseases are a group of genetic disorders c
Slide 41: Heavy patient burden with no approved therapies
Heavy patient burden with no approved therapies Presentation and Diagnosis Patients present to their primary care doctor and then often get referred to a neurologist for musculoskeletal issues Either the neurologist or a referral to a metabolic geneticist will result in a diagnosis Many patients are
Slide 42: KL1333 corrects the underlying pathophysiology
KL1333 corrects the underlying pathophysiology KL1333 normalizes conversation of NADH to NAD+ via NQO1 Normalizes the NAD+/NADH Ratio Restored Energy Metabolism Electron Transport Chain Complex III Complex IV Mitochondrial Membrane Q Synthase ATP Complex I Complex II X NADH NAD+ ADP + Pi ATP Restore
Slide 43: KL1333: First-in-disease small molecule with unique MOA
KL1333: First-in-disease small molecule with unique MOA Attributes Outcomes Directly increases the NAD+/NADH ratio Improved energy regulation and ETC via NQO1 function Unique MoA works upstream from all competing MoA in PMD Stimulation of mitochondria biogenesis Oral, small molecule, BID dosing Fati
Slide 44: Phase 1b demonstrated significant activity vs. placebo
Phase 1b demonstrated significant activity vs. placebo The placebo-controlled Phase 1b study demonstrated that KL1333 reduced patients’ fatigue and myopathy after only 10 days, 50 mg/day Fatigue Reduction Muscle Function Improvement Changes from baseline to day 10 Changes from baseline to day 10 KL1
Slide 45: Pivotal study design based on regulatory and patient advocacy input
Pivotal study design based on regulatory and patient advocacy input Study Schematic Regulatory Feedback Study Design Screening Both FDA and EMA accepted Methodology study as registrational • Randomized, double-blind, parallel-group, placebo- FDA said achieving one of the controlled pivotal study 3:2
Slide 46: Significant revenue opportunity for KL1333
Significant revenue opportunity for KL1333 PMD Prevalence 1 per 4,3001 US 78,200; EU4 and UK 76,400 Diagnosed mtDNA 9.6 per 100,0002 US 32,300; EU4 and UK 31,600 FALCON Trial Inclusion Criteria* 51% US 16,500; EU4 and UK 16,100 >30,000 diagnosed mtDNA mitochondrial disease patients addressable in th
Slide 47: Majority of patients diagnosed and treated in US Centers of Excellence
Majority of patients diagnosed and treated in US Centers of Excellence or academic institutions Mitochondrial Care Network – Centers: www.mitonetwork.org/centers 47
Slide 48: Other programs focus on different patient population or failed with different MOA
Other programs focus on different patient population or failed with different MOA Previous programs failed due to old mechanisms of action or evaluating the wrong endpoints Asset Type MOA / ROA Stage Patient Group Comments mtDNA mutations (e.g., NAD+/NADH ▪ Ongoing potentially registrational phase 2