Pharming Group Nv · EURONEXT:PHARM
Pharming Group Nv — Investor Day (February 2026)
110 slides from Pharming Group Nv's investor day presentation, Feb 3, 2026
Slide 1: Investor Day
Investor Day February 3, 2026 1
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: Disclaimer
Disclaimer This presentation has been prepared solely for informational purposes for the investor community. It is not intended to promote any product, provide medical or scientific advice, or influence prescribing, purchasing, or treatment decisions. Certain information in this presentation relates
Slide 4: Agenda
Agenda Welcome and introduction Fabrice Chouraqui, CEO Financial outlook 2026 Kenneth Lynard, CFO Q&A R&D overview: Pipeline and programs Anurag Relan, CMO Program 1: Jocelyn Farmer, MD, PhD. Lahey Hospital & Medical Center leniolisib for primary immunodeficiencies (PIDs) with immune dysregulation
Slide 5: Company overview
Company overview Fabrice Chouraqui, CEO 5
Slide 6: Combination of commercial and pipeline assets poised to deliver strong value creation
Combination of commercial and pipeline assets poised to deliver strong value creation Commercial Pipeline* RUCONEST® HAE (recombinant C1 esterase inhibitor) Differentiated value proposition Highly specific manufacturing process Joenja® (leniolisib) for APDS leniolisib for PIDs / CVID > $1B PIDs Sign
Slide 7: Vision for the future
Vision for the future Develop a leading global rare disease company with a diverse portfolio and presence in large markets, leveraging proven and efficient clinical development, supply chain, and commercial infrastructure 7 For investor audiences only
Slide 8: Strong commercial and financial momentum
Strong commercial and financial momentum Revenues Announced preliminary 2025 revenues* of $376M (+ 27%) – above latest guidance Amounts in US$ million Results reflect continued growth of RUCONEST® 376.0 and acceleration in Joenja® APDS uptake 297.2 Significant operating profit $30M and operating cas
Slide 9: Financial outlook 2026
Financial outlook 2026 Kenneth Lynard, CFO 9
Slide 10: Growth acceleration across the commercial portfolio
Growth acceleration across the commercial portfolio 27% YoY, 22% CAGR (2022-25) Revenues (US$ million) 376* Total revenues in $* millions 58 297 45 245 18 318 253 212 206 227 192 199 160 101 18 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 (Re-acquisition from Valeant) (Dec. 2016) RUCONEST® Joen
Slide 11: 2026 financial guidance and long-term capital outlook
2026 financial guidance and long-term capital outlook Revenue and operating expenses (in constant currency): FY 2026 Guidance Notes Total Revenues US$405 - 425 million • 8 - 13% growth • US$60 million incremental R&D investments to advance pipeline Operating Expenses US$330 - 335 million • US$9 mill
Slide 12: Thank You
Thank You Questions and Conversations 12
Slide 13: R&D overview: pipeline and programs
R&D overview: pipeline and programs Anurag Relan, CMO 13
Slide 14: Diverse rare disease portfolio and pipeline
Diverse rare disease portfolio and pipeline Phase III / registrational Regulatory Approval and Preclinical Phase I Phase II study submission commercialization Hereditary angioedema (HAE) RUCONEST® acute HAE Primary immunodeficiencies (PIDs) with immune dysregulation (Marketed in the U.S., U.K. - Eng
Slide 15: Executing on high value rare disease pipeline
Executing on high value rare disease pipeline Leniolisib sNDA for 4-11 yo APDS patients – requesting Type A meeting APDS Responded to CHMP (EMA) outstanding questions – potential 1H 2026 approval Japan and other regulatory reviews on track for 2026 approvals PIDs Genetic PID and CVID phase II POC tr
Slide 16: Agenda: leniolisib for PIDs with immune dysregulation
Agenda: leniolisib for PIDs with immune dysregulation PIDs with immune dysregulation have a considerable unmet need with large treatable population PI3Kδ is a master regulator of the immune system Leniolisib targets PI3Kδ and can modulate underlying immune dysregulation in PIDs Two multinational pha
Slide 17: The combined targeted population of the phase II studies plus APDS is ~44/million
The combined targeted population of the 2 phase II studies plus APDS is ~44/million All PIDs CVID with immune APDS is a PI3Kẟ driven monogenic disease within the CVID dysregulation PIDs with infectious with immune IUIS CVID classification acting as proof of concept for complications dysregulation on
Slide 18: Agenda: Napazimone (KL1333)
Agenda: Napazimone (KL1333) Primary mitochondrial diseases – rare disorders with significant unmet medical need Napazimone (KL13330 positioned to become first standard of care in mitochondrial DNA (mtDNA) disease Pivotal study ongoing with positive interim analysis confirming FDA-agreed primary endp
Slide 19: Disclaimer
Disclaimer The information and views presented by Dr. Jocelyn Farmer during this session are solely her own, derived from her clinical expertise and professional judgment. They do not necessarily represent or reflect the positions, perspectives, or official guidance of Pharming Group N.V. or any of
Slide 20: Leniolisib: Transforming Treatment of Immune Dysregulation in Primary Immunodeficiencies
Leniolisib: Transforming Treatment of Immune Dysregulation in Primary Immunodeficiencies Jocelyn Farmer, MD/PhD Associate Professor of Medicine, UMass Chan Medical School Director, Clinical Immunodeficiency Program, Beth Israel Lahey Health 20
Slide 21: Disclosures
Disclosures • Consulting: Pharming • Investigator-initiated research grants: • Pharming • Bristol Myers Squibb • Pfizer 21
Slide 22: Why am I speaking to you today?
Why am I speaking to you today? 22
Slide 23: About Me (Dr. Jocelyn Farmer)
About Me (Dr. Jocelyn Farmer): - MD/PhD in microbiology & immunology (University of Michigan) - Board-Certified Allergist/Immunologist (A/I Fellowship at Mass General) - Post-Doc at Ragon Institute in PI3K signaling impacting B cell biology (MIT, Harvard, Mass General) - Hired on at Beth Israel Lahe
Slide 24: What is PID? Why should you care about PID?
What is PID? Why should you care about PID? Primary Immunodeficiency (PID) 24
Slide 25: Primary Immunodeficiency = Unbalanced Immunity
Primary Immunodeficiency = Unbalanced Immunity Figure prompted by Farmer, JR; generated by ChatGPT 5.2, January 18, 2026, OpenAI, https://chat.openai.com
Slide 26: Which PID patients do we see in the clinic?
Which PID patients do we see in the clinic? APDS (rare) Most common PID = predominantly antibody deficiency (PAD) - APDS (activated PI3K-delta syndrome) rare PAD has FDA therapy (leniolisib) - CVID (common variable immunodeficiency) common PAD NO FDA therapy for immune dysregulation disease control
Slide 27: What is PID? Why should you care about PID?
What is PID? Why should you care about PID? Primary Immunodeficiency (PID) 27
Slide 28: No FDA-approved therapies to treat immune dysregulation in CVID
No FDA-approved therapies to treat immune dysregulation in CVID (No products currently in development except for leniolisib) Immune Infections Dysregulation Due to Antibody Deficiency Due to Immune Cell Auto-Reactivity Adequate control of infectious • No regulatory agency approved complications achi
Slide 29: Patients with CVID are dying from immune dysregulation
Patients with CVID are dying from immune dysregulation (11-fold higher risk of death with noninfectious complications) New York’s CVID cohort Germany’s CVID cohort Boston’s PAD cohort Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Blood. Bez P, Smits B, Geier C, Hirsch A, Caballero de Oyt
Slide 30: What do Patients with CVID Say?
What do Patients with CVID Say? “For decades I faced the systemic complexities of CVID without the benefit of any approved therapeutic treatment. It was a lonely and depressing predicament, knowing that my organs would never last long enough for me to see my sons grow up, and perhaps make me a grand
Slide 31: Can we apply clinical lessons from APDS to help CVID?
Can we apply clinical lessons from APDS (rare) to help the most patients with CVID (common)? 31
Slide 32: The clinical spectrum of CVID & APDS commonly overlap
Genetic APDS PI3Kδ-linked disorder gene Diagnosis (PIK3CD,PIK3R1) (NFKB, CTLA4, PTEN) unknown Diagnostic Testing The clinical spectrum of CVID & APDS commonly overlap Figure prompted by Farmer, JR; generated by ChatGPT 5.2, January 18, 2026, OpenAI, https://chat.openai.com
Slide 33: CVID = many underlying single genetic conditions
CVID = many underlying single genetic conditions Within genotyped CVID cohorts we find…. - APDS = rare in CVID - PI3Kδ-linked disorders = less rare in CVID (e.g., NFKB, CTLA4) - unknown gene = most patients with CVID J Hum Immun. 2025;2(1). doi:10.70962/jhi.20250157 Maffucci P, Filion CA, Boisson B,
Slide 34: The Clinical Presentations are Similar
The Clinical Presentations are Similar CVID APDS Diagram Adapted from APDS Symptoms | All about APDS Diagram Adapted from Baumann et. Al. Front. Immunol. August 2018 2 Blood (2012) 119 (7): 1650–1657. 34
Slide 35: The Clinical Presentations Cluster
The Clinical Presentations Cluster Unbiased Network Clustering of 75% of CVID Patients with Immune Dysregulation Exhibit an Noninfectious Disease Complications ‘APDS-like’ Endotype APDS disease spectrum overlaps significantly with CVID disease spectrum We have defined clinical complications within C
Slide 36: Can we apply biology learned from APDS to help CVID?
Can we apply biology learned from APDS (rare) to help the most patients with CVID (common)? 36
Slide 37: APDS, PI3Kδ-linked, CVID
APDS PI3Kδ-linked CVID PI3K CTLA4 PI3K PTEN ? PI3K NFKB1 ? ? leniolisib approved leniolisib Phase II leniolisib Phase II (7201) (8201) 37 Figure prompted by Farmer, JR; generated by ChatGPT 5.2, January 18, 2026, OpenAI, https://chat.openai.com
Slide 38: Shared in APDS, PI3Kδ-linked, and CVID disease: expansion of pathologic B cells
Shared in APDS, PI3Kδ-linked, and CVID disease: Expansion of pathologic B cells (CD21(lo), PI3K/mTOR(hi)) Healthy PI3Kδ- CVIDu CVIDc APDS Control linked Adapted from: Loss of B cell tolerance at the T2/T3a B cell transition is a convergent pathogenic mechanism in common variable immunodeficiency All
Slide 39: Convergent break in B cell tolerance causing end-organ disease
Shared in APDS, PI3Kδ-linked, and CVID disease: Convergent break in B cell tolerance causing end-organ disease APDS Healthy Loss of B cell tolerance at the T2/T3a B cell transition is a convergent pathogenic mechanism in common variable immunodeficiency Kirsty Hillier, Grace Yuen, Anson Hui, Suparna
Slide 40: Can we apply treatment from APDS to help CVID?
Can we apply treatment from APDS (rare) to help the most patients with CVID (common)? 40
Slide 41: Single Patient IND Experience in CVID
Single Patient IND Experience in CVID Demographics: 64-year-old female Immune Diagnosis: CVID (with unknown genetic cause) Life-threatening co-morbidities from CVID: chronic infections (sinus, lungs, skin), nodular regenerative hyperplasia (NRH) of liver, granulomatous and interstitial (GLILD) disea
Slide 42: Single Patient IND Experience in CVID
Single Patient IND Experience in CVID flow cytometry of stimulated B cells Healthy control Patient APDS PI3K-mTOR signaling by (p)S6 level 42 IND, Investigational New Drug
Slide 43: Single Patient IND Experience in CVID
Single Patient IND Experience in CVID Reduction in pathologic CD21(lo) B cells on leniolisib therapy over one year. 43 IND, Investigational New Drug
Slide 44: Single Patient IND Experience in CVID
Single Patient IND Experience in CVID Restoration of antibody-making switched memory (sm) B cells on leniolisib therapy over one year. 44 IND, Investigational New Drug
Slide 45: Single Patient IND Experience in CVID: Patient Perspective
Single Patient IND Experience in CVID: Patient Perspective “Leniolisib has given me hope that my immunological deficits can be stabilized and ultimately repaired. Dr. Farmer and her zealousness to obtain compassionate release of leniolisib has renewed my hope for the future and my longevity. Dreams
Slide 46: Acting With Urgency
Acting With Urgency Unlocking the potential of leniolisib to transform care for immune dysregulation in PIDs Rebecca Marsh, MD Medical Director 46
Slide 47: Disclaimer
Disclaimer Leniolisib is being investigated for a new indication that has not been approved by the FDA or any other regulatory authorities. The safety, efficacy, and appropriate use of leniolisib have not been established for this indication. There is no guarantee that this product will successfully
Slide 48: Our mission is to transform the care of additional PID patients
Our mission is to transform the care of additional PID patients with immune dysregulation This mission is well-founded, supported by: • Clear and significant patient need • Strong scientific rationale • Clinical experience from HCP- requested single patient IND treatment (N=6, 5 CVID)* 48 *Abstract
Slide 49: Pharming has developed clinical trials targeting PID disorders with immune dysregulation
Pharming has developed clinical trials targeting PID disorders with immune dysregulation under the influence of PI3K APDS Genetic PIDs Linked CVID With Immune (PIK3CD, PIK3R1) to PI3K Signaling Dysregulation 1 2 3 49 For investor audiences only
Slide 50: PI3Kδ is a master regulator of the immune system
PI3Kẟ is a master regulator of the immune system and imbalance contributes to immune dysregulation PI3Kẟ is a master regulator of Immune Shared pathology under the immune system and influences dysregulation pathology the influence of PI3K Lymphoproliferation p110δ APDS p85ɑ PI3Kδ AKT/PKB Autoimmuni
Slide 51: Pharming completed a phase III study in APDS leading to leniolisib approval
Pharming successfully completed a phase III study in APDS which led to the approval of leniolisib in APDS patients 12 years of age and older PI3Kẟ is a master regulator of APDS exemplifies a PID characterized by immune dysregulation and the immune system and influences serves as a proof-of-concept m
Slide 52: Leniolisib is a first-in-class medicine in APDS modulating PI3Kδ
Leniolisib is a first-in-class medicine in APDS and acts by modulating PI3Kẟ and consequently immune dysregulation PI3Kẟ is a master regulator of Pivotal study leading to multiple regulatory approvals showed leniolisib the immune system and influences has a significant impact on lymphadenopathy* Cha
Slide 53: Leniolisib may be transformative in additional PIDs with immune dysregulation
We believe leniolisib may be a transformative medicine in additional PIDs with immune dysregulation under the influence of PI3Kẟ PI3Kẟ is a master regulator of Immune Shared pathology under the immune system and influences dysregulation pathology the influence of PI3K Lymphoproliferation p110δ APDS
Slide 54: Phase II trials designed to evaluate safety, dosing, and impact on clinical manifestations
Our phase II trials are designed to evaluate safety, optimal dosing, and the impact of leniolisib on common/serious clinical manifestations Rates of Complications Impact of Complications on Mortality Average annual prevalence rate per 100,000 over the period 2004–2014. Odnoletkova I, Kindle G, Quint
Slide 55: Phase II proof of concept trial in genetic PIDs linked to PI3K signaling
Phase II proof of concept trial in ‘genetic PIDs linked to PI3K signaling’ Developed in collaboration with Dr. Gulbu Uzel, National Institutes of Health PTEN deficiency reduces PIP3 degradation, mimicking APDS-like PI3K activation (Tsujita et al., 2016). ALPS-FAS involves impaired apoptosis and enha
Slide 56: Phase II proof of concept trial in genetic PIDs linked to PI3K signaling
Phase II proof of concept trial in ‘genetic PIDs linked to PI3K signaling’ Developed in collaboration with Dr. Gulbu Uzel, National Institutes of Health PTEN deficiency reduces PIP3 degradation, mimicking APDS-like PI3K activation (Tsujita et al., 2016). ALPS-FAS involves impaired apoptosis and enha
Slide 57: Phase II proof of concept trial in genetic PIDs linked to PI3K signaling
Phase II proof of concept trial in ‘genetic PIDs linked to PI3K signaling’ 10mg 30mg 70mg Developed in collaboration with Dr. Gulbu Uzel • Single arm, open-label, dose range-finding Key exclusions: single center study at NIH (N=12) • Hematopoietic stem cell transplant • Dosing: 10/30/70 mg BID: • Im
Slide 58: Phase II proof of concept trial in CVID with Immune Dysregulation
Phase II proof of concept trial in ‘CVID with Immune Dysregulation’ Developed in collaboration with 10mg 30mg 70mg Dr. Jocelyn Farmer • Single arm, open-label, dose confirmation Key exclusions: multi-center study (N=20) • Hematopoietic stem cell transplant • Dosing: 10/30/70 mg BID: • Immunosuppress
Slide 59: Shared phase II objectives and endpoints support pivotal trial design
Shared phase II objectives and endpoints support pivotal trial design Objective: To assess safety and tolerability Objective: To evaluate the mechanistic impact of leniolisib; confirm dosing strategy of leniolisib Endpoints: AEs; PK/PD Endpoints: Phenotypic readouts of B cell maturation and other su
Slide 60: Epidemiology of genetic PIDs linked to PI3K signaling
Epidemiology of genetic PIDs linked to PI3K signaling* Diagnosed Current/future9 % Targeted for Genetic PID targeted Prevalence references prevalence estimate leniolisib type population (per million) treatment (per million) ESID registry (236 patients): 6 /mill.1 ALPS-FAS 5/10 30%3 3 PID KOLs – 4 /m
Slide 61: Epidemiology of CVID with immune dysregulation
Epidemiology of CVID with immune dysregulation: CVID patients numbering ~39/million may be APDS-like Targeted Total CVID with APDS-like CVID immune endotype Prevalence references (p/mill; dysregulation population median) (p/mill) (p/mill) ESID registry (4228 patients): 100 p/mill.1 USIDNET registry
Slide 62: Leniolisib could transform care for ~44/million PID patients
Leniolisib: we have the potential to transform care for ~44/million PID patients with immune dysregulation All PIDs 34.5/m CVID with immune CVID dysregulation PIDs with infectious with immune complications dysregulation only 4.5/m Genetic PIDs with immune dysregulation 1.5/m 3/m APDS 62 Diagram for
Slide 63: Summary: leniolisib for PIDs with immune dysregulation
Summary: leniolisib for PIDs with immune dysregulation PIDs with immune dysregulation have a considerable unmet need with large treatable population High mortality, no approved treatments or other products in development Combined target population ~44/million, significantly broader than APDS prevale
Slide 64: Thank You
Thank You Questions and Conversations 64
Slide 65: Agenda: Napazimone (KL1333)
Agenda: Napazimone (KL1333) Primary mitochondrial diseases – rare disorders with significant unmet medical need Napazimone (KL1333) positioned to become first standard of care in mitochondrial DNA (mtDNA) disease Pivotal study ongoing with positive interim analysis confirming FDA-agreed primary endp
Slide 66: Disclaimer
Disclaimer The information and views presented by Dr. Amel Karaa during this session are solely her own, derived from her clinical expertise and professional judgment. They do not necessarily represent or reflect the positions, perspectives, or official guidance of Pharming Group N.V. or any of its
Slide 67: Primary Mitochondrial Diseases
Primary Mitochondrial Diseases Amel Karaa, MD Director of the Mito Clinic Massachusetts General Hospital Harvard Medical School 67
Slide 68: Disclaimer
Disclaimer: The information presented are my own professional insights & considerations and not those of my employer, organization, committee or other group or individual I work with. 68 For investor audiences only
Slide 69: Mitochondrial disease is a distinct set of genetic metabolic disorders
Mitochondrial disease is a distinct set of genetic metabolic disorders International classification of inherited metabolic disorders 69 http://www.icimd.org/ For investor audiences only
Slide 70: Mitochondrial disease is a distinct set of genetic metabolic disorders
Mitochondrial disease is a distinct set of genetic metabolic disorders International classification of inherited metabolic disorders 70 http://www.icimd.org/ For investor audiences only
Slide 71: Mitochondrial disease is caused by mutations in mitochondrial or nuclear DNA
Mitochondrial disease is caused by mutations in either mitochondrial or nuclear DNA How is mitochondrial DNA different to nuclear DNA? The mitochondrial genome The mitochondrial genome is a circular DNA molecule that Chromosome contains approximately 16500 A chromosome is a single piece of bases and
Slide 72: Regina's story
Regina’s story Diagnosis: mitochondrial DNA myopathy (m.8344A>G) Family history: Brother and son with a very similar presentation. Daughter with a milder phenotype Symptoms: SNHL (using hearing aids), myoclonus, ataxia, dysarthria, ptosis, proximal myopathy, lipomatosis Treatments: exercise, dietary
Slide 73: Path to mitochondrial disease diagnosis (video 1)
Path to mitochondrial disease diagnosis (video 1) The videos featured can be viewed in the recording of the live event, which can be accessed here: https://www.pharming.com/pharming-investor-day-2026 73 For investor audiences only
Slide 74: Impact of mitochondrial disease (video 2)
Impact of mitochondrial disease (video 2) The videos featured can be viewed in the recording of the live event, which can be accessed here: https://www.pharming.com/pharming-investor-day-2026 74 For investor audiences only
Slide 75: Multifactorial diagnostic evaluation centered around genetic testing
Multifactorial diagnostic evaluation centered around genetic testing Biochemistry Genetic Testing Lactate, pyruvate mtDNA sequencing CPK, aldolase GDF-15/FGF-21 Nuclear panels Metabolic profiling WES WGS Tissue pathology RRF COX (-)/SDH (+) fibers CoQ10 levels End-Organ Assessments Heart Kidney Davi
Slide 76: Mitochondrial disease is progressive and impacts mortality
Mitochondrial disease is progressive and impacts mortality over the course of life Mortality by decade Commun Biol 6, 22 (2023) Ivaniuk et al. Neurology 2025 Feb 25;104(4):e209779 76 For investor audiences only
Slide 77: Mitochondrial disease impairs mitochondrial function
Mitochondrial disease impairs mitochondrial function Increased Mitochondrial ROS levels Impaired Mitochondrial trafficking Defective Mitochondrial Biogenesis Mito Dysfunction Altered Mitochondrial Dynamics Defective Mitophagy Dysfunctional OXPHOS Metabolism 77 Li et al. Metabolites. 2021 Apr 10;11(4
Slide 78: Mitochondrial diseases have diverse clinical implications
Mitochondrial diseases have diverse clinical implications 78 Vafai and Mootha, Nature 2012 For investor audiences only
Slide 79: Mitochondrial disease symptoms
Mitochondrial disease symptoms Muscle weakness and debilitating fatigue are among the most frequently reported mitochondrial disease symptoms in adults across studies • Two of the highest frequency symptoms in the North American Disease Consortium (NAMDC) registry* • Two most frequent and prioritize
Slide 80: Fatigue in mitochondrial disease has a high impact on quality of life
Fatigue in mitochondrial disease has a high impact on quality of life and functional abilities Fatigue characteristics Fatigue impacts PROMIS® Fatigue Mitochondrial Disease Short Form Validated scale to assess mitochondrial disease fatigue symptoms and impacts on daily life Some In the past 7 days…
Slide 81: Mitochondrial disease is a common uncommon disease
Mitochondrial disease is a common uncommon disease Category Estimated Worldwide Count Pathogenic mtDNA variant carriers (genetic) ~32–40 million Clinically manifest mtDNA disease (all variants) ~0.8–1.6 million Clinically manifest m.3243A>G disease ~300,000–400,000 Clinically manifest single large-s
Slide 82: Limited treatment and management options
Limited treatment and management options Minimize energy losses Optimize energy Avoid stressors gains Adequate rest Restorative Sleep Nutrition Exercise 82 For investor audiences only
Slide 83: A range of potential therapeutic approaches
A range of potential therapeutic approaches Antioxidants/RedOx Nitric Oxide modulators Targets of Mitophagy Membrane stabilizers Idebenone L-citrulline IW-6463 API-009 Elamipretide PTC743 (EPI734) L-arginine Sildenafil Rapamycin Sonlicromanol OMT-28 Targets of Biogenesis Gene Therapy NAD+/NADH ratio
Slide 84: Two recent approvals in ultra rare subsets of mitochondrial disease
Two recent approvals in ultra rare subsets of mitochondrial disease 84 For investor audiences only
Slide 85: Established US mitochondrial community
Established US mitochondrial community US Patient Organizations Driving awareness, research, educations and support Patients, health care professionals and research audiences Centers of excellence and expert networks in US Annual disease conferences – Monthly education series Mitochondrial Care netw
Slide 86: Thank you
== Mass EH) MASSACHUSETTS fF} HARVARD + General ‘eau’, GENERAL HOSPITAL GY uniweesiry Brigham Thank you
Slide 87: Napazimone (KL1333) for primary mitochondrial disease
Napazimone (KL1333) for primary mitochondrial disease Magnus Hansson, MD, PhD Executive Medical Director 87
Slide 88: Disclaimer
Disclaimer Napazimone (KL1333) is investigational drug and has not been approved for use by any regulatory authority. Its safety and efficacy have not been established, and it is currently under clinical evaluation. There is no guarantee that this drug will receive regulatory approval or become comm
Slide 89: Napazimone designed to target underlying pathology in mtDNA mitochondrial disease
Napazimone (KL1333) designed to target the underlying pathology in mtDNA mitochondrial disease Dysfunctional mitochondria Napazimone (KL1333) is designed to target the underlying pathology by restoring NAD+/NADH ratio: mtDNA mutations Impaired OXPHOS OXPHOS NADH NAD+ Low NAD+/NADH ratio Decreased en
Slide 90: Napazimone is designed to restore NAD+/NADH ratio and energy production
Napazimone (KL1333) is designed to restore NAD+/NADH ratio and energy production Normal cellular energy production is In mitochondrial disease, pathogenic variants Napazimone (KL1333) is designed to restore regulated by the balance of NAD+/NADH in mtDNA impact OXPHOS complex synthesis energy product
Slide 91: In vitro, napazimone restores NAD+/NADH ratio in MELAS fibroblasts
In vitro, napazimone (KL1333) restores NAD+/NADH ratio and mitochondrial biogenesis in MELAS patient fibroblasts NAD+/NADH Mitochondrial mass ETC protein ETC activity Seo et al. 2018. KL1333, a Novel NAD+ Modulator, Improves Energy Metabolism and Mitochondrial Dysfunction in MELAS Fibroblasts 91 (ht
Slide 92: In a phase Ia/b study, napazimone demonstrated positive changes in outcome measures
In a phase Ia/b study, napazimone (KL1333) demonstrated positive changes in outcome measures Reduction of fatigue Improvement in muscle function Biomarker changes Changes from baseline to day 101 Changes from baseline to day 101 Lactate: Pyruvate ratio1 Improvement Improvement 1. Pizzamiglio C et al
Slide 93: Napazimone effects on biomarkers demonstrate target engagement
Napazimone (KL1333) effects on disease biomarkers demonstrate target engagement at anticipated exposure levels A PopPK model was developed from 3033 observations in KL1333 Exposure and changes in lactate and lactate: pyruvate 42 healthy participants and 6 patients with PMD in phase ratio had a clear
Slide 94: Napazimone MoA has potential to address high unmet need of mtDNA mitochondrial disease
Napazimone (KL1333) MoA has the potential to address high unmet need of mtDNA mitochondrial disease HCPs n=16 (US) Unmet Need in mitochondrial disease No 6.4 High (Scale 1-7) Unmet Need 1 2 3 4 5 6 7 Unmet Need “Most patients, unfortunately, don’t have a cure. They have a way of dealing with the iss
Slide 95: Pivotal study program targets a specific but common subset of adult mitochondrial disease
Napazimone (KL1333) pivotal study program targets a specific but common subset of adult Mitochondrial Disease which can be diagnosed with a genetic test International Classification of Inborn Metabolic Disorders (ICIMD) ICIMD category Category 6 – Mitochondrial DNA- related disorders • Impairs OXPHO
Slide 96: mtDNA variants targeted in pivotal program cause the majority of adult disease
mtDNA variants targeted in pivotal program cause the majority of adult disease Three pathogenic variants of mtDNA causes >50% of adult mitochondrial disease m.3243A>G caused disease accounts for about 35% of all adult mitochondrial disease mtDNA Single Most patients have mixed phenotypes, The Single
Slide 97: Napazimone clinical trial design to enable first-in-class treatment
Napazimone (KL1333) clinical trial design to enable first-in-class treatment Pivotal FALCON Trial Phase I a/b study1 - Efficacy & safety evaluation2 Open-label extension study Randomized, blinded, placebo- Randomized, blinded, Nonrandomized, open-label, controlled patient cohort placebo-controlled l
Slide 98: Pivotal FALCON study design de-risks program
Pivotal FALCON study design de-risks program MAIN STUDY (48 weeks) Follow-up RANDOMIZATION (5 weeks) SCREENING STUDY END Napazimone (KL1333) Treatment (tablets twice daily) Placebo Week -8 to -12 Week 24 Week 48 Week 53 Screening / Run-in Interim Futility Primary Safety Follow-up Analysis Efficacy A
Slide 99: Interim analysis results further de-risked pivotal study
Interim analysis results further de-risked pivotal study Positive outcome achieved, with both primary endpoints having passed futility Promising differences favoring the active arm vs. placebo for both primary efficacy endpoints; if trends continue consistently, we expect a successful result at the
Slide 100: Napazimone has demonstrated a benign safety profile
Napazimone (KL1333) has demonstrated a benign safety profile in phase 1 studies and FALCON wave 1 Phase 1 Single Ascending Dose study (101) Phase 1 Drug-Drug Interaction study (103) No Serious Adverse Events (SAEs) Weak inhibitor of CYP1A2 Mild dose-dependent gastrointestinal (GI) AEs at high Neglig
Slide 101: Incorporating lessons learned from previous programs
Incorporating lessons learned from previous programs Previous studies likely failed due to mechanism of action not targeting a critical underlying cause of disease, using a mixed patient population (e.g., mtDNA + nDNA) or using insensitive endpoints Napazimone (KL1333) Boicedelpar Mavodelpar Sonlicr
Slide 102: Napazimone Target Product Profile attractive to HCPs and patients
Napazimone (KL1333) Target Product Profile based on FALCON study attractive to HCPs and patients Willingness to prescribe product X HCPs n=16 Not at 6.4 Extremely all willing willing 1 2 3 4 5 6 7 • HCPs see mechanism as rational and likely to be efficacious because of the nicotinamide adenine dinuc
Slide 103: Significant addressable patient population for napazimone
Significant addressable patient population for napazimone (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 pa
Slide 104: Summary: Napazimone (KL1333)
Summary: Napazimone (KL1333) Primary mitochondrial diseases – rare disorders with significant unmet medical need Severe fatigue, myopathy (muscle weakness), and reduced life expectancy Poor quality of life (e.g., loss of job, social isolation, depression) Napazimone (KL1333) positioned to become fir
Slide 105: Thank You
Thank You Questions and Conversations
Slide 106: Building momentum across commercial, financial and pipeline
Building momentum across commercial, financial and pipeline Strong growth Strategic growth High value Building a leading rare momentum priorities pipeline disease company 2025 revenue ~$376M: Sustained growth of Joenja® (leniolisib) for Growth-oriented leadership • High dbl-digit growth for commerci
Slide 107: Thank You
Thank You Questions and Conversations
Slide 108: www.pharming.com
www.pharming.com NASDAQ: PHAR | EURONEXT Amsterdam: PHARM
Slide 109: Epidemiology of genetic PIDs linked to PI3K signaling: references
Epidemiology of genetic PIDs linked to PI3K signaling References: 1. Based on 1.4% of PID patients reported as ALPS in the ESID registry & overall PID prevalence of 1/2500. 2. Median from survey of 7 PID KOL opinions. 3. Most ALPS-FAS patients are well treated, with 30% in need of better treatment (
Slide 110: Epidemiology of CVID with immune dysregulation: references
Epidemiology of CVID with immune dysregulation CVID patients numbering ~39/million may be APDS-like References: 1. Based on overall PID prevalence of 1/2500, with 26% of PID patients reported as CVID in the ESID registry 2. Based on overall PID prevalence of 1/2500 with 33% of PID patients reported