Slides
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NASDAQ: PHAR | EURONEXT Amsterdam: PHARM Pharming Group N.V. Jefferies Global Healthcare Conference June 4-5, 2025
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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 results, performance, or events to differ materially from those expressed or implied in these statements. These forward-looking statements are identified by their use of terms and phrases such as “aim” , “ambition” , ‘‘anticipate’’ , ‘‘believe’’ , ‘‘could’’ , ‘‘estimate’’ , ‘‘expect’’ , ‘‘goals’’ , ‘‘intend’’ , ‘‘may’’, “milestones” , ‘‘objectives’’ , ‘‘outlook’’ , ‘‘plan’’ , ‘‘probably’’, ‘‘project’’ , ‘‘risks’’ , “schedule” , ‘‘seek’’, ‘‘should’’ , ‘‘target’’ , ‘‘will’’ and similar terms and phrases. Examples of forward-looking statements may include statements with respect to timing and progress of Pharming's preclinical studies and clinical trials of its product candidates, Pharming's clinical and commercial prospects, and Pharming's expectations regarding its projected working capital requirements and cash resources, which statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to the scope, progress and expansion of Pharming's clinical trials and ramifications for the cost thereof; and clinical, scientific, regulatory, commercial, competitive and technical developments. In light of these risks and uncertainties, and other risks and uncertainties that are described in Pharming's 2024 Annual Report and the Annual Report on Form 20-F for the year ended December 31, 2024, filed with the U.S. Securities and Exchange Commission, the events and circumstances discussed in such forward-looking statements may not occur, and Pharming's actual results could differ materially and adversely from those anticipated or implied thereby. All forward-looking statements contained in this presentation are expressly qualified in their entirety by the cautionary statements contained or referred to in this section. Readers should not place undue reliance on forward- looking statements. Any forward-looking statements speak only as of the date of this presentation and are based on information available to Pharming as of the date of this presentation. Pharming does not undertake any obligation to publicly update or revise any forward- looking statement as a result of new information, future events or other information. 2
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Fabrice Chouraqui appointed as new CEO Pharming completes acquisition of Abliva Positive topline data in leniolisib APDS pediatric trial History of growth and innovation at Pharming 3 Pharming acquires leniolisib for APDS 2019 2010 2014 FDA accepts priority review of NDA for leniolisib 2022 FDA approves RUCONEST® EMA approves RUCONEST® 2023 2024 FDA approves Joenja® 2016 Pharming initiates acquisition of Abliva RUCONEST®: 10-years approval in the U.S. Pharming reacquires RUCONEST North American commercialization rights UK MHRA approves Joenja® 2025 Start of Phase II trial of leniolisib for CVID with immune dysregulation Start of Phase II trial of leniolisib for PIDs with immune dysregulation Final NICE guidance and Joenja® launch in England and Wales Australia TGA approves Joenja®
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4 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
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Building a leading global rare disease biopharma company Strong start to 2025 • 1Q25 revenues up 42% • Strong RUCONEST® growth and acceleration of Joenja® patient uptake • Achieved operating profit (adjusted non-GAAP) • Raised 2025 revenue guidance to US$325-340M • Optimize capital allocation through $10M annual G&A reduction 5 High value pipeline • 2 assets with >$1B sales potential each • Joenja® (leniolisib) for PIDs with immune dysregulation - Genetic PIDs - CVID • KL1333 for mtDNA mitochondrial disease - Registrational trial ongoing Significant catalysts • Joenja® for APDS – VUSs reclassification, pediatric label, geo expansion (2025-27) • Leniolisib for PIDs PhII readouts (2026) • KL1333 pivotal study readout (2027)
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• Continued strong RUCONEST® growth • Acceleration in Joenja® patient uptake • Raised 2025 revenue guidance to US$325-340 million • Achieved operating profitability (adj. non-GAAP) and positive operating cash flow 6 1Q 2024 1Q 2025 Amounts in US$ million Revenues (16.3) 0.8 Amounts in US$ million Adjusted (Non-GAAP) Operating profit (loss)* 1Q 2024 1Q 2025 55.6 79.1 * Adjusted operating profit for 1Q 2025 excludes US$7.8 million of non-recurring Abliva acquisition-related expenses. Strong first quarter 2025 performance
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RUCONEST® strong growth continues in acute HAE market 7 • Strong U.S. in-market demand ₋ Continuing to add prescribers and patients ₋ New patient enrollments remain high (>90) • Continued robust U.S. volume growth ₋ Quarterly growth +37% ₋ 1Q25 boosted by lower inventory at the SPs in 4Q24 & faster prior authorizations 46.0 68.6 1Q 2024 1Q 2025 Amounts in US$ million RUCONEST® revenues
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Joenja® growth continues in 12y+ APDS segment 8 • Increasing APDS patients on therapy ₋ 102 U.S. patients (+23% vs 1Q24) ₋ Acceleration in patient uptake (+6 in 1Q25, most since 2Q24) • 18% volume growth • Launched in U.K. (England and Wales) in April • Additional 187 APDS patients globally in access programs and clinical studies 9.6 10.5 1Q 2024 1Q 2025 Amounts in US$ million Joenja® revenues
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9 Diverse rare disease pipeline
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RUCONEST® for HAE
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RUCONEST® (rhC1INH): 2nd most prescribed therapy for acute HAE attacks in the US 11 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
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Type 1, Type 2, and Normal C1-INH HAE patients rely on RUCONEST 97% patients needed just 1 dose1 93% acute attacks stopped for at least 3 days2 RUCONEST® mostly used by patients experiencing moderate to severe attacks, who attack more frequently • Fail on icatibant and other acute therapies • Need to re-dose with other treatments to resolve attacks RUCONEST® unique value proposition 12 Time of taking RUCONEST 4 hours after 24 hours after References: 1. RUCONEST®. Prescribing information. Pharming Healthcare Inc; 2020. 2. Bernstein JA, et al. Ann Allergy Asthma Immunol. 2017;118(4):452-453. 3. Data on file. Pharming Healthcare Inc; 2019 The most common adverse reactions (incidence ≥2%) were headache, nausea and diarrhea. The most serious adverse reaction reported in clinical trials was anaphylaxis.
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Joenja® (leniolisib) for APDS leniolisib for PIDs with Immune Dysregulation
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Joenja®: immune modulator that targets the root cause of APDS Helps address immune deficiency and immune dysregulation Joenja® facilitates a balanced PI3Kδ pathway to support proper immune function6 14 Note: Illustration does not include all steps in the signaling pathway. p110δ p85α Immature/senescent cells Functional cells This is a graphical representation of a complex biological process. AKT/PKB, protein kinase B; FOXO, forkhead box O; mTOR, mammalian target of rapamycin; p85α, the regulatory subunit of the PI3Kδ enzyme; p110δ, the catalytic subunit of the PI3Kδ enzyme. 1. Fruman DA, et al. Cell. 2017;170(4):605-635. 2. Okkenhaug K, Vanhaesebroeck B. Nat Rev Immunol. 2003;3(4):317-330. 3. Hoegenauer K, et al. ACS Med Chem Lett. 2017;8(9):975-980. 4. Rao VK, et al. Blood. 2017;130(21):2307-2316. 5. Rao VK, et al. Blood. 2023;141(9):971-983. 6. Nunes-Santos CJ, et al. J Allergy Clin Immunol. 2019;143(5):1676-1687. JOENJA WAS DESIGNED TO TARGET THE ROOT CAUSE OF APDS TO HELP NORMALIZE THE HYPERACTIVE PI3Kδ PATHWAY1-5
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Rao VK, et al. Blood Adv. 2024;8(12):3092-3108. doi:10.1182/bloodadvances.2023011000. 24-year-old male with APDS whose progress was followed in the Joenja® open-label extension study for 6 years Reports of Joenja® changing patients’ lives 15
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16 Joenja® (leniolisib) Lifecycle to realize $1Bn+ sales potential Joenja® for PIDs with immune dysregulation linked to PI3Kδ signaling Phase II trial ongoing Joenja® for CVID with immune dysregulation Phase II trial ongoing Joenja® marketed in the U.S.*, U.K. (England and Wales) Europe/ROW access programs Genetic PIDs prevalence +7.5 patients / million Potential total prevalence ~40 patients / million APDS prevalence ~1.5 patients / million Targeted geographic expansion Reclassification of VUS patients (2H25 growth lever) Pediatric label expansion leniolisib new indications: PIDs with immune dysregulationJoenja (leniolisib) for APDS * 102 patients on paid therapy. U.S. Pricing: 30-day supply $49,500, Annual cost (WAC) $594,000
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17 Joenja®: Reclassification of VUS patients * As results become available, patients with validated variants could be diagnosed with APDS and be eligible for Joenja® treatment. Variants of Uncertain Significance >1300 patients in the US with VUS test result VUSs: insufficient data to determine if variant is disease causing With additional data, up to 20% of VUS results could be reclassified as disease causing for APDS* High throughput screening (MAVE) study completed, identifying many new variants causing PI3Kδ hyperactivity Data to be published shortly (submitted and under review) Genetics testing labs will review study data, reclassify variants, and update test reports. Expected positive impact from reclassifications later this year VUS Resolution Steps
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Indication expansion (additional PIDs) Pediatric expansion (APDS) 18 Joenja® development status Expanding the addressable patient population Geographic expansion (APDS) Europe – review extended to Jan. 2026 Single outstanding CMC request Positive clinical benefit and safety concluded U.K. – Marketing authorization 2024 Reimbursement: NICE positive final guidance and England / Wales launch Apr. 2025 AUS approval, CAN regulatory review Australia - approved Mar. 2025 Canada decision in 2026* Japan clinical study: Patient enrolment complete, positive interim analysis PMDA filing mid-2025 4 to 11 years – Positive data presented at CIS conference in May U.S. FDA filing planned 3Q 2025 1 to 6 years – Patient enrolment completed in April 2025 PIDs with immune dysregulation linked to PI3Kδ signaling Phase II trial ongoing CVID with immune dysregulation Phase II trial ongoing Other country regulatory approvals/filings Access Programs * Anticipate regulatory action in 2026 for Canada
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All PIDs PIDs with immune dysregulation Genetic PIDs with immune dysregulation CVID Infectious complications only CVID with immune dysregulation APDS 19 Leniolisib for PIDs with immune dysregulation Not to scale with population sizes Rationale • Critical role of PI3Kδ in lymphocyte regulation, driving lymphoproliferation and autoimmunity • Same therapeutic strategy as in APDS: modulate PI3Kδ to address immune dysregulation • Positive experience in compassionate use patients Two Phase II studies underway • Genetically defined PIDs with immune dysregulation1 • Common variable immunodeficiency (CVID) with immune dysregulation2 • Topline results mid-2026 1. PIDs include ALPS-FAS, CTLA4 haploinsufficiency, NFKB1 haploinsufficiency and PTEN deficiency, amongst others. Prevalence 7.5 patient s / million 2. Prevalence 39 patients/million Patient Population • PID patients with clinical manifestations similar to APDS, including early mortality • Significant unmet clinical need, no approved therapies • Large group: Prevalence 5-26x APDS
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KL1333 for mtDNA Mitochondrial Disease
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21 KL1333 for primary mitochondrial disease: Potential first standard of care “The fatigue is almost impossible to describe because it seems other-worldly. It feels as though someone has taped cinder blocks to my eyelids some mornings and there is no way to keep them open.”2 KL1333 targets underlying pathology of low NAD+ / NADH • Normalizes NAD+/NADH ratio and mitochondrial function, with evidence from in vitro data, animal models, and in patients treated with KL1333 • >30,000 diagnosed patients with mitochondrial DNA disease potentially addressable by KL13331 Registrational clinical study underway • Clinically-relevant endpoints, supported by FDA • Positive interim analysis in pivotal study • Patient recruitment for second wave started April 2025 • Expect readout in 2027 and FDA approval end of 2028 1. In US, EU4 and UK. Diagnoses can include MELAS-MIDD and KSS-CPEO spectrum disorders as well as MERRF syndrome. 2. UNITED MITOCHONDRIAL DISEASE FOUNDATION, Voice of the Patient Report, 2019.
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22 KL1333 – FALCON study positive interim analysis 180 total patients treated for 48 weeks • Wave 1 sites ready to start enrolling • Wave 2 sites undergoing activation Readout anticipated 2027 WAVE 1 – Fully enrolled Interim Futility Analysis: 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 completion of this trial Data monitoring committee (DMC) recommended continuing with Wave 2: • Safety and tolerability profile acceptable • No changes to study design • 180 total patients confirmed in the study WAVE 2 – Expansion 40 patients recruited across six countries (U.S., UK, France, Spain, Belgium, Denmark) 18 sites activated Interim analysis at 24 weeks conducted in Q3 2024 Pivotal FALCON Study
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Financials and Outlook
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(10.5) (11.8) Amounts in US$ million Net profit (loss) (16.2) (8.6) Amounts in US$ million Adjusted (Non-GAAP) Operating profit (loss)* * Operating profit (loss) for 2023 excludes milestone payments for Joenja® (US$10.5 million) and gain on sale of Priority Review Voucher to Novartis (US$21.3 million). ** US$30.4 million of the US$45.6 million decrease in overall cash and marketable securities is due to convertible bond refinancing. 24 227.1 252.2 18.2 45.0 FY 2023 FY 2024 Amounts in US$ million Revenues RUCONEST Joenja Financial highlights: FY 2024 vs FY 2023 220.1 261.8 FY 2023 FY 2024 Amounts in US$ million Gross profit 68.9 83.1 55.9 70.7 124.0 118.8 FY 2023 FY 2024 Amounts in US$ million OpEx development R&D G&A M&S 248.8 272.6 215.0 169.4 December 31, 2023 December 31, 2024 Amounts in US$ million Overall cash and marketable securities** 245.3 297.2 FY 2023 FY 2024FY 2023 FY 2024
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46.0 68.6 9.6 10.5 1Q 2024 1Q 2025 Amounts in US$ million Revenues RUCONEST Joenja 25 Financial highlights: 1Q 2025 vs 1Q 2024 47.2 70.8 1Q 2024 1Q 2025 Amounts in US$ million Gross profit 18.5 21.1 15.1 22.5 30.2 34.6 1Q 2024 1Q 2025 Amounts in US$ million OpEx development* R&D G&A M&S 63.8 78.2 (16.3) 0.8 Amounts in US$ million Adjusted (Non-GAAP) Operating profit (loss)* (12.4) (14.9) Amounts in US$ million Net profit (loss) 169.4 108.9 December 31, 2024 March 31, 2025 Amounts in US$ million Overall cash and marketable securities** 55.6 79.1 1Q 2024 1Q 2025 * Adjusted operating profit for 1Q 2025 excludes US$7.8 million of non-recurring Abliva acquisition-related expenses (US$5.7 million in G&A, $2.1 million in R&D). ** Decrease in cash primarily driven by purchases of Abliva shares totaling US$66.1 million. 1Q 2024 1Q 2025
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26 2025 Financial guidance FY 2025 Guidance Notes Total Revenues US$325 - 340 million 9 - 14% growth Operating Expenses (pre-Abliva impact) Flat vs. FY 2024 Operating Expenses (Abliva-related) ~US$30 million Includes R&D and non-recurring transaction and integration costs Revenue and operating expenses: Available cash and future cash flows expected to cover current pipeline investments and pre-launch costs
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Building a leading global rare disease biopharma company Strong start to 2025 • 1Q25 revenues up 42% • Strong RUCONEST® growth and acceleration of Joenja® patient uptake • Achieved operating profit (adjusted non-GAAP) • Raised 2025 revenue guidance to US$325-340M • Optimize capital allocation through $10M annual G&A reduction 27 High value pipeline • 2 assets with >$1B sales potential each • Joenja® (leniolisib) for PIDs with immune dysregulation - Genetic PIDs - CVID • KL1333 for mtDNA mitochondrial disease - Registrational trial ongoing Significant catalysts • Joenja® for APDS – VUSs reclassification, pediatric label, geo expansion (2025-27) • Leniolisib for PIDs PhII readouts (2026) • KL1333 pivotal study readout (2027)
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NASDAQ: PHAR | EURONEXT Amsterdam: PHARM www.pharming.com
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Pharming Group N.V. Appendix
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30 APDS is a rare primary immunodeficiency (PID) Genetic defect leads to PI3Kδ hyperactivity Hyperactive PI3Kδ results in dysregulated B and T cell development1-3 The PI3Kδ enzyme is at the beginning of a complex signaling pathway Bcell / T cell PI3Kδ p110δ p85ɑ AKT/PKB FOXO mTOR Growth Survival Differentiation Proliferation Apoptosis inhibition Note: Illustration does not include all steps in the signaling pathway. Immune imbalance leads to diverse signs and symptoms1,4-6 Severe, recurrent, persistent infections • Sinopulmonary • Herpesvirus (especially EBV and CMV) Lymphoproliferation • Lymphadenopathy • Splenomegaly/hepatomegaly • Nodular lymphoid hyperplasia Enteropathy Autoimmunity • Cytopenias • Autoimmune disorders • Autoinflammatory disorders Lymphoma Bronchiectasis FOXO, forkhead box O; mTOR, mammalian target of rapamycin; PI3Kδ, phosphoinositide 3-kinase delta; PKB, protein kinase B. 1. Lucas CL, et al. Nat Immunol. 2014;15(1):88-97. 2. Fruman DA, et al. Cell. 2017;170(4):605-635. 3. Okkenhaug K, Vanhaesebroeck B. Nat Rev Immunol. 2003;3(4):317-330. 4. Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606. 5. Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218. 6. Jamee M, et al. Clin Rev Allergy Immunol. 2020;59(3):323-333.
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31 APDS can impact many facets of life Physical1,2 Frequent infections Swollen glands Shortness of breath Coughing/wheezing Chest or joint pain Fatigue Inability to exercise Hearing loss Diarrhea Skin problems Mental1,3-5 Anxiety Depression Stress Treatment Burden1-4 Frequent hospitalizations Surgeries Visiting multiple doctors Invasive or time- consuming treatments Social3,4 Missing school, work, or daily activities APDS, activated phosphoinositide 3-kinase δ syndrome. 1. Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606. 2. Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218. 3. Rider NL, et al. J Clin Immunol. 2017;37(5):461-475. 4. Jiang F, et al. Allergy Asthma Clin Immunol. 2015;11:27. 5. Kuburovic NB, et al. Patient Prefer Adherence. 2014;8:323-330.
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32 Heterogeneous, evolving symptomology can often lead to missed diagnoses Improved identification of symptoms, increased genetic testing, and earlier diagnosis are needed APDS has often been diagnosed as another PI or condition, causing delays in diagnosis1 *Pathologies can occur at any time. †In Elkaim APDS2 cohort, median age of bronchiectasis is 13; in Maccari ESID cohort, median age is 11.2. ‡No median ages are available for these manifestations. ALPS, autoimmune lymphoproliferative syndrome; CID, combined immunodeficiency; CVID, common variable immune deficiency; ESID, European Society for Immunodeficiencies; HIGM, hyper immunoglobulin M syndrome; IgG, immunoglobulin G; PI3Kδ, phosphoinositide 3-kinase delta; XLA, X-linked agammaglobulinemia. 1. Jamee M, et al. Clin Rev Allergy Immunol. 2020;59(3):323-333. 2. Maccari ME, et al. Front Immunol. 2018;9:543. 3. Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218.e9. 4. Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606. Timeline of the most common pathologies* seen in APDS1-4 Sinopulmonary infections Enteropathy Cytopenias, arthritis, or other dysregulation‡ 3 years (range,1-6 years) 5 years (range,1-18 years) 10.5 years (range,6-15 years) 11.2 years† (range,18 months-39 years) 18 years (range,1.5-40 years) Median age at diagnosis: 12 years (7-year median diagnosis delay) <1 year (range,1 month-10 years) Benign lymphoproliferation Autoimmunity Bronchiectasis Malignancy ALPS 1 XLA 1 Hyper IgM 11 Lymphoma 8CVID 6 CID 6 Recurrent infections 4 IgG subclass deficiency 2
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No drug-related serious adverse events or study withdrawals in Joenja® trials Clinical data and tolerability for long term treatment 33 Joenja®: First and only approved therapy for APDS Joenja® (leniolisib) is an oral medication used to treat activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older Joenja® targets the root cause of APDS • Normalizes the hyperactive PI3Kδ pathway to correct the underlying immune defect in APDS patients • Helps address both immune deficiency and immune dysregulation Approved in the US (Mar 2023), Israel (Apr 2024), UK (Sept 2024), Australia (Mar 2025) Regulatory reviews on-going in the EU, Canada and several other countries Submission planned in Japan in 2025 Please see Important Safety Information and full Prescribing Information available at joenja.com Rao VK, et al. Blood. 2023;141(9):971-983 Rao VK, et al. Poster presented at:64th Annual American Society of Hematology Annual Meeting; December 10-13, 2022; New Orleans, LA.
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34 Management for APDS1,2 prior to Joenja® Immune Deficiency Immune Dysregulation • Antimicrobial prophylaxis • Immunoglobulin replacement therapy • Corticosteroids • Other immunosuppressants • mTOR inhibitors Hematopoietic stem cell transplant None of these therapies are FDA- approved for APDS treatment APDS, activated phosphatidylinositol 3-kinase δ syndrome; IRT, immunoglobulin replacement therapy; mTOR, mammalian target of rapamycin; PI, primary immunodeficiency; PIRD, primary immune regulatory disorder. 1. Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606. 2. Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218. 3. Chan AY, et al. Front Immunol. 2020;11:239. 4. Chinn IK, et al. J Allergy Clin Immunol. 2020;145(1):46-69.
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35 Joenja® clinical trial designs bid, twice a day; PI3Kδ, phosphoinositide 3-kinase delta; SPD, sum of product diameters 1. Rao VK, et al. Blood. 2017;130(21):2307-2316. 2. NCT02435173. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02435173. Updated May 6, 2015. Accessed March 13, 2023. 3. Rao VK, et al. Blood. 2023;141(9):971-983. 4. NCT02859727. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02859727. Updated October 31, 2022. Accessed March 3, 2023. 5. Data on file. Pharming Healthcare Inc; 2022. Pivotal Trial - Part 1: Dose- finding1,2 Pivotal Trial - Part 2: Efficacy & Safety Evaluation3 Open-label extension study4,5 6 patients with APDS 12 weeks 10 mg, 30 mg, 70 mg bid (4 weeks each dose) 70 mg bid selected for Part 2 31 patients with APDS (21 Joenja®, 10 placebo) Co-primary efficacy end points • Change from baseline in log10-transformed SPD of index lesions • Also assessed as % change • Change from baseline in percentage of naïve B cells out of total B cells Secondary and exploratory end points Safety Nonrandomized, open-label, dose-escalating Randomized, triple-blinded, placebo-controlled • 35 patients with APDS from Parts 1 and 2 • 2 patients with APDS previously treated with investigational PI3Kδ inhibitors Ongoing 70 mg bid Long-term safety, tolerability, efficacy, and pharmacokinetics Nonrandomized, open-label, long-term study 12 weeks 70 mg bid
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36 Joenja® addresses the underlying cause of APDS to help restore immune balance – Phase 3 co-primary endpoints -10 0 10 20 30 40 50 CFB at D85 in Naïve B Cells/Total B Cells, % Data were analyzed using an ANCOVA model with treatment as a fixed effect and baseline as a covariate. Use of glucocorticoids and IRT at baseline were both included as categorical (Yes/No) covariates. Baseline is defined as the arithmetic mean of the baseline and D1 values when both are available, and if either baseline or the D1 value is missing, the existing value is used. P-value is 2-sided. Least square means are graphed. Error bars are standard error of the mean. *The analysis excluded 2 patients from each treatment group due to protocol deviations and 1 Joenja patient having complete resolution of the index lesion identified at baseline. †Out of 27 patients in the PD analysis set, 13 patients met the analysis requirements, including having a percentage of <48% of naïve B cells at baseline, to form the B-PD analysis set. Joenja [package insert]. Leiden, The Netherlands: Pharming Technologies B.V.; 2023. Please see Important Safety Information and full Prescribing Information available at joenja.com Change from baseline in naïve B cells† n=8 n=5 Joenja Placebo p=0.0002 Change from baseline in index nodes* Joenja Placebo n=18 n=8 Immune Deficiency Immune Dysregulation 21 x 16 mm 12 x 9 mm Prior to Treatment After 12 Weeks p=0.0006 -46% -5% 37% 0.1% Log10-transformed SPD of index lesions Joenja (n=18) Placebo (n=8) Baseline mean (SD) 3.03 (0.42) 3.05 (0.39) Change from baseline, LS mean (SE) -0.27 (0.04) -0.02 (0.05) Difference vs placebo (95% CI) -0.25 (-0.38, -0.12) At 12 weeks Joenja® decreased lymphadenopathy and increased naïve B cells
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37 Secondary endpoint: Significant reductions in spleen size by 2D and 3D analysis compared to placebo • The adjusted mean difference in bidimensional spleen size between Joenja® (n=19) and placebo (n=9) was -13.5 cm2 (95% CI: -24.1, -2.91), P=0.0148 • The adjusted mean difference in 3D spleen volume between Joenja® (n=19) and placebo (n=9) was -186 cm3 (95% CI: -297, -76.2), P=0.0020 Joenja® significantly reduced splenomegaly Rao VK, et al. Blood. 2023;141(9):971-983. *In the PD analysis set, the mean (SD) percentage change from baseline to week 12 in 3D spleen volume (mm3) was -26.68% (12.137) with Joenja® (n=19) and -1.37% (24.238) with placebo (n=9). The ANCOVA model was used with treatment as a fixed effect and log10-transformed baseline as a covariate for index and non-index lesions. The use of both glucocorticoids and IV Ig at baseline was included as categorical (yes/no) covariates. This analysis excluded 2 patients in each treatment group. In the Joenja® group, 1 patient with a complete index lesion response was excluded, and 3 patients were excluded for no non-index lesion at baseline. PD, pharmacodynamics. at week 12 27% reduction in 3D spleen volume* Secondary measure: spleen volume scan results of actual patient illustrate average improvement documented for patients taking Joenja® Prior to treatment: 491 mL At week 12: 314 mL Actual patient images of a 17-year-old male. As individual results vary, images may not be representative of all patients.
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38 • In the Joenja® arm, IgM was elevated above normal limits in 6 patients at baseline, and by week 12 was reduced in all, with 50% returning to within normal limits • In contrast, IgM was elevated above normal limits at baseline in 4 patients in the placebo arm, and by week 12 levels remained stable or elevated, with 0% returning to within normal limits An exploratory endpoint showed Joenja® reduced IgM levels Error bars are standard error of the mean. Safety analysis set (N=31) shown. Blue box indicates IgM normal range. Soluble biomarkers, including IgM, were prespecified exploratory endpoints in the protocol. Although an observational decrease in IgM was noted in some patients, no statistical significance can be made from this analysis, and no conclusions should be drawn. Rao VK, et al. Blood. 2023;141(9):971-983 Mean serum IgM rapidly reduced to within normal limits 0 100 400 600 IgM, mg/dL Baseline 21 10 n n Joenja® Placebo Week 4 20 10 Week 8 21 10 Week 12 21 10 Normal range
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39 Joenja® safety profile A patient with multiple occurrences of an AE is counted only once in the AE category. Only AEs occurring at or after first drug intake are included. *Includes dermatitis atopic and eczema. †Includes tachycardia and sinus tachycardia. AEs, adverse events; ALT, alanine aminotransferase; AST, aspartate aminotransferase; SAE, serious adverse event. 1. Rao VK, et al. Blood. 2023;141(9):971-983. 2. Joenja [package insert]. Leiden, The Netherlands: Pharming Technologies B.V.; 2023. 3. Data on file. Pharming Healthcare Inc; 2022. Please see Important Safety Information and full Prescribing Information available at joenja.com • Study drug-related AEs occurred in 8 patients; the incidence was lower in the Joenja arm (23.8%) than in the placebo arm (30.0%) • No AEs led to discontinuation of study treatment Phase 3 Trial1,2 Adverse reactions reported by ≥2 patients treated with Joenja and more frequently than placebo Joenja (n=21) n (%) Placebo (n=10) n (%) Headache 5 (24) 2 (20) Sinusitis 4 (19) 0 Dermatitis atopic* 3 (14) 0 Tachycardia† 2 (10) 0 Diarrhea 2 (10) 0 Fatigue 2 (10) 1 (10) Pyrexia 2 (10) 0 Back pain 2 (10) 0 Neck pain 2 (10) 0 Alopecia 2 (10) 0 Open-label Extension Study3 Data cutoff for interim analysis: December 13, 2021 • 38 patients had a median exposure of ~2 years • 4 patients had >5 years of exposure • 32/37 patients reported ≥1 AE • 78.4% of AEs were grade 1, 48.6% grade 2, 27.0% grade 3, 0% grade 4 • No SAEs related to Joenja Across all trials2 Most common AEs n Upper respiratory tract infection 8 Headache 6 Pyrexia 6 Otitis externa 5 Weight increase 5 COVID-19, positive/negative 5/14 One patient with significant baseline cardiovascular comorbidities suffered cardiac arrest resulting in death at extension Day 879; determined by investigator not to be related to study drug
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40 Open-label extension interim analysis of days spent with infections and IRT reduction *Infections that developed during the study were reported as adverse events. Investigators were requested to inquire about signs and symptoms of infections at each visit, with a particular focus on bacterial enterocolitis. Patients were not provided an infection diary to document infections occurring between visits. One patient was excluded from the analysis due to an incorrect year that was recorded for an infection. †Baseline infections are each group’s year 1 annual rate of infections. N values changed because patients were in the OLE for different lengths of time. ‡Data on concomitant medication usage was reported at each patient visit. §One patient had a subsequent one-time dose. ||One patient achieved IRT freedom for 3 months but subsequently restarted IRT. IRT, immunoglobulin replacement therapy; m, number of infection days; N, number of patients in follow-up category. Rao VK, et al. Poster presented at: 64th Annual American Society of Hematology Annual Meeting; December 10-13, 2022; New Orleans, LA. Please see Important Safety Information and full Prescribing Information available at joenja.com Although safety was the primary objective of the open-label study, this post hoc analysis from the open-label study was not powered to provide any statistical significance of efficacy and therefore no conclusions should be drawn. 42.4 13.8 8.7 5.5 0 5 10 15 20 25 30 35 40 45 ≥ 1 year of follow-up ≥ 2 years of follow-up ≥ 3 years of follow-up ≥ 4 years of follow-up ≥ 5 years of follow-up N=28 N=14 N=7 N=4 0 N=3 Baseline† 26.7 Baseline† 38.5 Baseline† 22.9 Baseline† 39.0 Days with infection per patient (m/N) Annual Rate of Infection Days* Physician-reported IRT Reduction‡ 6 achieved IRT freedom§ Of 27 patients receiving IRT: 3 reduced use 50%|| 1 reduced use 30% At the data cutoff, 4 of the patients who were IRT free had been so for 1 – 2.5 years 37% OF PATIENTS RECEIVING IRT REDUCED OR DISCONTINUED DOSE
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RUCONEST Pediatric Phase III trial for children 4-11 years old with APDS 41 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 adolescents and adults Benefits seen across the four tested dose levels No deaths/discontinuations due to AEs. No new safety findings Data to be presented at CIS conference in May Regulatory filings beginning with the U.S. in second half 2025 Pediatric APDS clinical trial results support regulatory filings
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VUS by the numbers Pharming is aware of ~1,300 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) variants • Similar VUS frequencies expected worldwide • Published literature, which includes more than 1.5 million patients, showed that 20% of reclassified VUSs are upgraded to LP/P • Pilot study in 25 VUS patient samples - findings consistent with APDS identified in 5 patients (20%) including patient preparing for enrollment 42 No systemic initiatives exist to resolve PIK3CD/R1 VUSs, yet these patients remain a significant opportunity to identify incremental patients with APDS VUSs frustrate patients and doctors, limiting diagnosis of genetic diseases such as APDS ~1,200
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Given importance of PI3Kδ in B & T cells, immune dysregulation in PIDs can occur via alterations in PI3Kδ signaling Bcell / T cell p110δ p85ɑ AKT/PKB FOXO mTOR Growth Survival Differentiation Proliferation Apoptosis inhibition PI3Kδ Note: Illustration does not include all steps in the signaling pathway. Clinical manifestations, disease onset and severity similar to APDS 5-10 Infections • Sinopulmonary • Herpesvirus Lymphoproliferation • Lymphadenopathy • Splenomegaly/hepatomegaly • Nodular lymphoid hyperplasia GI Disease • Autoimmune enteropathy • Nodular regenerative hyperplasia Autoimmunity • Cytopenias • Autoimmune disorders • Autoinflammation Lymphoma Pulmonary Disease • GLILD • Bronchiectasis FOXO, forkhead box O; mTOR, mammalian target of rapamycin; PI3Kδ, phosphoinositide 3-kinase delta; PKB, protein kinase B. 1. Volkl et al. Blood 2016; 128(2):227-238. 2. Tsujita, et al. J Allergy Clin Immunol. 2016;138(6):1872-80. 3. Rowshanravan B, et al. Blood. 2018;131(1):58-67. 4. Additional unpublished collaborator data. 5. Bride K & Teachey D. F1000Res. 2017;6:1928 6. Kuehn HS, et al. Science 2014; 345:1623-27. 7. Lorenzini T, et al. J Allergy Clin Immunol. 2020:146:901-11. 8. Eissing, et al. Transl Oncol. 2019;12(2):361-3672. 9. Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606. 10. Schwab C, et al. J Allergy Clin Immunol. 2018;142(6):1932-1946. High unmet medical need - no approved therapies other than Joenja® (leniolisib) for APDS: SOC immunosuppressives (e.g. rapamycin) have limited efficacy and significant tolerability concerns Altered PI3Kδ signaling can occur in multiple PID genetic disorders beyond APDS (ex: ALPS-FAS, CTLA4, NFKB1, PTEN) 1-4 leniolisib 43
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Leniolisib for PIDs with immune dysregulation – Phase II studies • Single arm, open-label, dose range-finding (N=20) • Patients with a CVID diagnosis, evidence of lymphoproliferation, and at least one additional clinical manifestation of immune dysregulation • Primary: Safety & Tolerability • Secondary/Exploratory: PK/PD, efficacy measures • 10/30/70 mg BID: 4/4/16 wks treatment, respectively • Multi-center study (US, UK, EU) • Lead investigator: Jocelyn Farmer, MD, PhD, Director of the Clinical Immunodeficiency Program (Beth Israel Lahey Health) 44 • Single arm, open-label, dose range-finding (N=12) • Patients with PIDs linked to PI3Kδ signaling, e.g. ALPS-FAS1, CTLA4 haploinsufficiency2, NFKB1 haploinsufficiency3, PTEN deficiency4 • Primary: Safety & Tolerability • Secondary/Exploratory: PK/PD, efficacy measures • 10/30/70 mg BID: 4/4/12 wks treatment, respectively • Lead investigator: Gulbu Uzel, M.D., Senior Research Physician, Co-Investigator: V. Koneti Rao, M.D., FRCPA, Senior Research Physician, Primary Immune Deficiency Clinic (ALPS Clinic) (NIH) 1. Bride K & Teachey D. F1000Res. 2017;6:1928. ; Rao VK & Oliveria JB. Blood 2011; 118(22):5741-51. 2. Kuehn HS, et al. Science 2014; 345:1623-27. ; Schwab C, et al. J Allergy Clin Immunol. 2018;142(6):1932-1946. 3. Lorenzini T, et al. J Allergy Clin Immunol. 2020:146:901-11. 4. Eissing M, et al. Transl Oncol. 2019;12(2):361-367. ; Tsujita, et al. J Allergy Clin Immunol. 2016;138(6):1872-80. Genetically defined PIDs with immune dysregulation linked to PI3Kδ Common variable immunodeficiency (CVID) with immune dysregulation
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NAD: Nicotinamide adenine dinucleotide; NADH: Nicotinamide adenine dinucleotide + hydrogen; ETC: Electron transport chain. 45 Dysfunctional mitochondria produce less ATP Primary Mitochondrial Disease (PMD) Mitochondria, often described as the “powerhouses” of cells, are crucial for energy production Mitochondrial diseases are a group of genetic disorders characterized by dysfunctional mitochondria due to mutations in mitochondrial (mtDNA) or nuclear DNA The abnormal NAD+/NADH ratio results in decreased ATP production, contributing to organ dysfunction and disease deterioration For patients this means symptoms of severe fatigue and muscle weakness – symptoms which patients report as the most troublesome* Dysfunctional Mitochondria Mutation Impaired ETC protein expression NAD+ ATPNADH Impaired NAD+/NADH ratio Decreased energy production Decreased mitochondria biogenesis *Voice of the Patient Report, United Mitochondrial Disease Foundation, 2019.
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46 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 diagnosed at academic centers specializing in mitochondrial disease A combination of routine lab tests and genetic testing available from major testing labs help to diagnose patients Heavy patient burden with no approved therapies Presentation and Diagnosis Impact Patients heavily burdened in their daily lives including symptoms like severe fatigue, myopathy, and metabolic dysfunction Impact on QoL including loss of job, loss of independence, depression/anxiety Primary mitochondrial diseases lead to a three-to-four-decade reduction in life-expectancy Treatment No approved treatment options Patients are limited to using vitamins, supplements, and physical therapy “ On the worst days I will be crying in frustration because going to the kitchen seems equivalent to climbing a mountain and just trying to process what others are saying to me involves all the energy and concentration that I have.” United Mitochondrial Disease Foundation, Voice of the Patient Conference, 2019
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47 Normalizes the NAD+/NADH Ratio Restored Energy Metabolism KL1333 corrects the underlying pathophysiology Restored energy regulation and improved ETC function Stimulation of mitochondria biogenesis Overall resulting in symptom reduction and expected disease modification Electron Transport Chain KL1333 normalizes conversation of NADH to NAD+ via NQO1 ATP Mitochondrial Membrane Complex I Complex II Complex III ATP Synthase Complex IV NADH NAD+ ADP + Pi Q X NADH NAD+ KL1333 KL1333- H2 NQO1
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48 KL1333: First-in-disease small molecule with unique MOA Directly increases the NAD+/NADH ratio via NQO1 Unique MoA works upstream from all competing MoA in PMD Oral, small molecule, BID dosing Favourable safety profile Favourable IP protection Orphan Drug Designation in US & EU and FDA Fast Track Potential first-in-disease with registrational clinical study Improved energy regulation and ETC function Stimulation of mitochondria biogenesis Fatigue reduction Increased exercise capacity Attributes Outcomes
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49 KL1333 demonstrated efficacy in the phase 1b placebo- controlled portion with patients diagnosed with mtDNA mitochondrial disease Phase 1b demonstrated significant activity vs. placebo Fatigue Reduction Changes from baseline to day 10 Muscle Function Improvement Changes from baseline to day 10 The placebo-controlled Phase 1b study demonstrated that KL1333 reduced patients’ fatigue and myopathy after only 10 days, 50 mg/day Source: Pizzamiglio C et al., Optimizing rare disorder trials: a phase 1a/1b randomized study of KL1333 in adults with mitochondrial disease, Brain, 2024. Lactate:Pyruvate Ratio Changes from baseline to day 10 • Fatigue reduction (NeuroQoL fatigue change) • Muscle function improvement (30 seconds sit-to-stand) KL1333 showed efficacy signals after 10 days using 50 mg/day Mitochondrial patients have increased lactate levels and increasing the concentration of KL1333 resulted in an improved lactate/pyruvate ratio, reflecting target engagement No serious adverse events reported
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50 Pivotal study design based on regulatory and patient advocacy input Methodology Patients Included Primary Endpoints Study Schematic Both FDA and EMA accepted study as registrational FDA said achieving one of the two endpoints would be sufficient for filing Conducted regular and detailed discussions with the FDA to facilitate alignment Regulatory Feedback Study Design • Fatigue using the PROMIS Fatigue Mitochondrial Disease Short Form • Muscle weakness using the 30 second Sit-to-Stand test • Adult PMD patients with mtDNA mutations* with fatigue and myopathy • Randomized, double-blind, parallel-group, placebo- controlled pivotal study *Most prevalent mtDNA disorders include m.3243A>G associated MELAS-MIDD spectrum disorders, single large scale mtDNA deletion associated KSS-CPEO spectrum disorders, other multisystemic mtDNA-related disease (including MERRF) Screening 3:2 Randomization KL1333 Placebo Open Label ExtensionWeek 53 Safety follow-up Week 24 Interim futility analysis (Wave 1 only) Week 48 Primary efficacy analysis
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51 FALCON study – positive interim analysis 180 total patients treated for 48 weeks • Wave 1 sites ready to start enrolling • Wave 2 sites undergoing activation Readout anticipated 2027 WAVE 1 – Fully enrolled Interim Futility Analysis: 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 completion of this trial Data monitoring committee (DMC) recommended continuing with Wave 2: • Safety and tolerability profile acceptable • No changes to study design • 180 total patients confirmed in the study WAVE 2 – Expansion 40 patients recruited across six countries (U.S., UK, France, Spain, Belgium, Denmark) 18 sites activated Interim analysis at 24 weeks conducted in Q3 2024 Pivotal FALCON Study
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52 Significant revenue opportunity for KL1333 1 Gorman, G.S. et al. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol 2015 May;77(5):753-9. 2 Gorman, G.S. et al. Mitochondrial Diseases. Nat. Rev. Vol 2, 1-22 (2016). *mtDNA mutations including m.8344A>G MELAS-MIDD, MERRF, KSS-CEPO, large scale mtDNA deletions >30,000 diagnosed mtDNA mitochondrial disease patients addressable in the US, EU4 and UK 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
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53 Majority of patients diagnosed and treated in US Centers of Excellence or academic institutions Mitochondrial Care Network – Centers: www.mitonetwork.org/centers
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54 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 KL1333 Small molecule NAD+/NADH modulator Oral Pivotal mtDNA mutations (e.g., mtDNA deletion, m.8344A>G, MELAS-MIDD, MERRF, KSS-CEPO) ▪ Ongoing potentially registrational phase 2 study ▪ FALCON pivotal study reported positive 24w interim analysis Elamipretide Peptide Cardiolipin stabilizer Subcutaneous Phase 3 nDNA mutations ▪ nDNA represents about 20% of PMD patients ▪ In discussions with FDA for ultra rare Barth syndrome Zagociguat Small molecule Guanylate cyclase stimulator Oral Phase 2b ready MELAS ▪ Completed open-label MELAS phase 2a ▪ Phase 2b trial planned with focus on fatigue, myopathy and cognition Sonlicromanol Small molecule Redox modulator Oral Phase 3 ready mtDNA mutation (MELAS- MIDD) ▪ Phase 2a study in m.3243A>G patients showed predominantly neutral results across multiple endpoints ▪ Phase 2b study failed primary endpoint, positive changes in post-hoc analyses and open-label extension Mavodelpar Small molecule PPARδ agonist Oral NA mtDNA in the interventional trial and extended to include nDNA in the OLE Phase 3 failed to achieve primary endpoint of 12-minute walk test Boicedelpar Small molecule PPARδ agonist Oral NA Mixed population of mtDNA and nDNA Phase 2 program using 6-minute walk test terminated
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55 Income statement Balance sheet • Cash purchases of Abliva shares totaling US$66.1 million • Recognized intangible asset related to KL1333 (US$63.1 million), goodwill (US$13.4 million) and deferred tax liabilities (US$12.8 million) • Other net identifiable assets were not significant and were recognized at fair value Abliva acquisition – first quarter financial impact Amounts in US$m 1Q 2025 1Q 2024 Revenues 79.1 55.6 Cost of Sales (8.3) (8.4) Gross profit 70.8 47.2 Other income 0.4 0.3 Research and development* (21.1) (18.5) General and administrative* (22.5) (15.1) Marketing and sales (34.6) (30.2) GAAP operating profit (loss) (7.0) (16.3) + non-recurring Abliva acquisition-related expenses* 7.8 - Adjusted (Non-GAAP) operating profit (loss) 0.8 (16.3) * US$7.8 million of non-recurring Abliva acquisition-related expenses in 1Q 2025 (US$5.7 million in General and administrative and US$2.1 million in Research and development expenses).