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gsk.com gsk.com 17 December 2024 Meet GSK management R&D focus for the next-wave of pipeline Interactive event for investors and analysts. This webinar is being recorded.
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2 This presentation may contain forward-looking statements. Forward-looking statements give the Group’s current expectations or forecasts of future events. An investor can identify these statements by the fact that they do not relate strictly to historical or current facts. They use words such as ‘anticipate’, ‘estimate’, ‘expect’, ‘intend’, ‘will’, ‘project’, ‘plan’, ‘believe’, ‘target’ and other words and terms of similar meaning in connection with any discussion of future operating or financial performance. In particular, these include statements relating to future actions, prospective products or product approvals, future performance or results of current and anticipated products, sales efforts, expenses, the outcome of contingencies such as legal proceedings, dividend payments and financial results. Other than in accordance with its legal or regulatory obligations (including under the Market Abuse Regulations, UK Listing Rules and the Disclosure Guidance and Transparency Rules of the Financial Conduct Authority), the Group undertakes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Investors should, however, consult any additional disclosures that the Group may make in any documents which it publishes and/or files with the US Securities and Exchange Commission (SEC). All investors, wherever located, should take note of these disclosures. Accordingly, no assurance can be given that any particular expectation will be met and investors are cautioned not to place undue reliance on the forward-looking statements. Forward-looking statements are subject to assumptions, inherent risks and uncertainties, many of which relate to factors that are beyond the Group’s control or precise estimate. The Group cautions investors that a number of important factors, including those in this presentation, could cause actual results to differ materially from those expressed or implied in any forward-looking statement. Such factors include, but are not limited to, those discussed under Item 3.D ‘Risk factors’ in the Group’s Annual Report on Form 20-F for the full year (FY) 2023. Any forward-looking statements made by or on behalf of the Group speak only as of the date they are made and are based upon the knowledge and information available to the Directors on the date of this presentation. A number of adjusted measures are used to report the performance of our business, which are non-IFRS measures. These measures are defined and reconciliations to the nearest IFRS measure are available in the Group’s Q3 2024 Results and the Group’s Annual Report on Form 20-F for FY 2023. All expectations, guidance and outlooks regarding future performance and the dividend should be read together with the section “Guidance and outlooks, assumptions and cautionary statements on page 54 of our stock exchange announcement of the Group’s Q3 2024 Results, the section “Assumptions and basis of preparation related to 2024 guidance” in the Appendix of this presentation and the statements on page 317 of the Group’s Annual Report on Form 20-F for FY 2023. Cautionary statement regarding forward-looking statements
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3 Participants Dr Tony Wood Chief Scientific Officer Speakers Q&A Luke Miels Chief Commercial Officer Dr Hesham Abdullah SVP, Global Oncology R&D Dr Kaivan Khavandi SVP, Global Respiratory/Immunology R&D
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4 Next Wave of R&D Our R&D approach is paving the way for a pipeline of best/first in class medicines and vaccines to deliver growth at scale to 2030 and beyond Unique understanding of the role of fibrosis and auto-inflammation Precision approaches to identify the right target, the right treatment and the right patient Interventions that support healthy immune system ageing Our R&D approach is paving the way for a pipeline of best/first in class medicines and vaccines to deliver growth at scale to 2030 and beyond Deeper expertise in the science of the immune system Competitive and differentiated technologies Network of world-class partnerships and complimentary BD
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Our focus for today: Oncology and Respiratory/Immunology Respiratory/Immunology Build on decades of knowledge in inflammatory mechanisms… …to lead in COPD1 and target fibrotic lung, liver and kidney disease. Oncology Expand beyond our current focus in haematological and gynaecological cancers… …with antibody drug- conjugates (ADCs) for the treatment of solid tumours. 5
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Oncology
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7 1. Second line. 2. Data presented at ASH 2024. 3. Standard of care. 4. Overall survival. Blenrep could redefine treatment in 2L1 multiple myeloma with exceptional efficacy, manageable safety profile and advantageous ease of administration Transformational patient benefit Sustained overall survival advantage seen as early as four months Safety and tolerability consistent with known profile Eye-related side effects: transient, reversible and manageable with dose modifications and delays Administration in community setting Filed in 7 countries; US decision expected July 2025 DREAMM-7: statistically significant 42% reduction in risk of death vs. SoC2,3 Median OS4 was not reached. Predicted median OS based on modeling was 84 months for BVd and 51 months for DVd
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8 1. First line. 2 Data presented at the 5th European Myeloma Network Meeting, April 2024. 3. Lifecycle innovation. 4. Minimal residual disease. 5. Progression free survival. Promising early results in newly diagnosed patient cohorts increase confidence in Blenrep 1L1 and further lifecycle innovation DREAMM-10 to initiate this month with initial results expected H2 2027 Newly diagnosed multiple myeloma N=520 Primary endpoints: MRD 4 negativity, PFS5 Phase I/II BelaRd Study2 100% response rate in newly diagnosed patients DRd (daratumumab, lenalidomide, dexamethasone) BRd (belamaf, lenalidomide, dexamethasone) R 1:1 Oncologic Drugs Advisory Committee (ODAC) has voted unanimously in favour of MRD negativity testing as an early endpoint in multiple myeloma Phase III DREAMM-10: Blenrep in 1L multiple myeloma study design Rapid, deep, and durable responses across cohorts No disease progression observed in newly diagnosed patients at 24.8 months median follow up Actively exploring LCI3 opportunities in line with competitive developments
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9 1. Tumour tissue = tumour cells or stroma. Modified from Seaman et al. 2017; Lung (SCLC); Carvajal Hausdorf et al. 2019. 2. Antibody drug conjugate. 3. Chemistry, manufacturing and control. ADCs targeting B7-H3 provide multi-indication, transformational potential B7-H3 is broadly expressed across multiple tumours1 ADC2 design targets and kills tumour cells, sparing healthy tissue Development opportunity in genitourinary, lung, gastrointestinal and beyond Builds on Blenrep progress and CMC3 capabilities Complements existing and emerging portfolio B7-H3 antibody (Fc region, hlgG1) B7-H3 antibody (Fab region) Cytotoxic TOPO1i payload (N=4) Significant emerging opportunity
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10 1. Wang J, Duan J, Xing L, et al. ARTEMIS-001: Phase 1 study of HS-20093, a B7-H3–targeting antibody-drug conjugate, in patients with advanced solid tumor. J Clin Oncol. 2023;41 (suppl 16):3017. doi:10.1200/JCO.2023.41.16_suppl.3017). 2. Response Evaluation Criteria in Solid Tumours. GSK5764227 (B7-H3 ADC) has broad impact across multiple tumour types Promising clinical data across multiple tumour types GSK’227 showed anti-tumour responses in a range of solid tumours All patients heavily pretreated Substantial activity even at low doses Safety profile manageable; side effects in line with those commonly observed in cancer treatment GSK’227 has broad clinical activity across solid tumours 1 Assessed according to RECIST2 1.1 by investigators.
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11 1. ARTEMIS-001 results presented at 2024 World Lung Conference. Data cut-off date: 30 June 2024. 2. Demedts et al. European Respiratory Journal 2009 35(1): 202-215. 3. Objective response rate. 4. Disease control rate GSK’227 Breakthrough Designation based on 50-61% overall response rate in extensive-stage small-cell lung cancer1 and significant need for improved treatments ES-SCLC SoC has an expected response rate <20%2 8.0 mg/kg (n=31) 10.0 mg/kg (n=22) ORR3, % (95% CI) 61.3 (42.2, 78.2) 50.0 (28.2, 71.8) DCR4, % (95% CI) 80.6 (62.5, 92.5) 95.5 (77.2, 99.9) Best Percent Change of Target Lesions in 53 Tumour Evaluable Patients 40 20 0 - 20 - 40 - 60 - 80 * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Best Change From Baseline in Target Lesion Size (%) 8.0 mg/kg 10.0 mg/kg Percent Change of Target Lesion Size over Time in 53 Tumour Evaluable Patients
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12 1. Kinnear K et al. Clin Cancer Res. 2023;29:1086–101. 2. SEER: 5-year survival statistics for distant metastatic disease in US. 3. Triple negative breast cancer. 4. Poly(ADP-ribose) polymerase inhibitors. 5. Homologous recombination proficient. 6. Endometrial cancer. GSK5733584 (B7-H4 ADC) could redefine survival outcomes in ovarian and endometrial cancer B7-H4 widely expressed across solid tumours1 ADC design enables targeted treatment Significant emerging opportunity Highly expressed across multiple tumours, at very low levels in healthy tissue Emerging clinical profile suggests best-in-class potential Builds on existing expertise and capability, complementing Zejula and Jemperli • Tackles platinum & PARPi4 resistance, and HRp5 tumours in ovarian cancer • Combination with Jemperli in EC6, replacing chemo 5-year survival for patients with distant metastasis2 18% Endometrial 4% Choliangio- carcinoma 32% Ovarian 13% TNBC3 B7-H4 antibody (Fc region, hlgG1) Cytotoxic TOPO1i payload B7-H4 antibody (Fab region)
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13 1. Overall response rate. 2. Kinneer K, et al. Clin Cancer Res. 2023;29:1086–1101. *Includes China, Macau, Hong Kong and Taiwan 3. Triple negative breast cancer. . GSK’584 shows promising proof of concept with combination potential GSK’584 showed an ORR1 of 33.3% (4.8 mg/kg) and 27.3% (5.8mg/kg) in TNBC patients2,3 0.7 mg/kg 1.4 mg/kg 4.8 mg/kg 5.8 mg/kg 7.2 mg/kg 80 60 40 20 0 –20 –40 –60 –80 Best change from baseline in target lesion size (%) Substantial activity even at low doses and in heavily pretreated patients Manageable safety profile, side effects in line with those commonly observed in cancer treatment Exploring activity in other gynaecologic cancers Development focus on GSK proprietary combinations, including Jemperli Proof of concept study under way to support future pivotal programme; expect results in H2 2025
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14 1. Colorectal cancer. 2. Head and neck squamous cell carcinoma. 3. Small cell lung cancer. . Accelerating GSK’227 (B7-H3 ADC) and GSK’584 (B7-H4 ADC) development, with first phase III results expected in 2027 GSK’584 (B7-H4) prioritiesGSK’227 (B7-H3) priorities Development in lung, CRC1, HNSCC2, prostate, and other solid tumours Updated SCLC3 and osteosarcoma data (Hansoh) at ASCO 2025 GSK global dose-escalation study at ESMO 2025 Pivotal studies start: Q4 2025 Close collaboration with Hansoh, multi-regional trials Development as monotherapy and in combination across multiple indications in ovarian and endometrial cancers Data in ovarian and endometrial cancer at ASCO 2025/ ESMO 2025 Dose expansion data anticipated in 2025 External collaborations in early-stage breast cancer in 2025 Pivotal studies start: 2026
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15 ADCs enable expansion into a range of solid tumours with significant unmet need, strengthening our current portfolio and unlocking new combination potential ADCs could disrupt conventional treatment regimens, alone and in combination with PD1s2, complementing Jemperli development and replacing chemotherapy in later lines Gynaecologic Lung GI1 Head & neck Breast Jemperli GSK’227 (B7-H3) GSK’584 (B7-H4) 1. Gastro-intestinal 2. Programmed cell death protein 1.
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16 MM: multiple myeloma, CRC: colorectal cancer, HNSCC: head and neck squamous cell carcinoma, NSCLC: non-small cell lung cancer. SCLC: small cell lung cancer. H&N: head and neck. Timelines are illustrative. With accelerated development, ADCs approvals could come 2027+ Estimated approval timelines across Immuno-oncology portfolio Haematologic Gynaecologic Lung GI Other tumours Launched 2025 2026 2027+ Ojjaara Myelofibrosis Jemperli Endometrial (RUBY Part 1) Zejula Ovarian cobolimab NSCLC (COSTAR+dostar) Jemperli Colon, rectal (AZUR 1&2) B7-H3 ADC CRC B7-H3 ADC SCLC B7-H4 ADC Endometrial, Ovarian Blenrep 2L+ MM (DREAMM-7/8) Blenrep 1L MM (DREAMM-10) belrestotug (TIGIT) Lung (GALAXIES 301 + dostar) Jemperli HNSCC (JADE) B7-H4 ADC Breast belrestotug (TIGIT) (GALAXIES H&N + dostar) Jemperli + Zejula (FIRST) Ovarian
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Respiratory/Immunology
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18 1. Chronic obstructive pulmonary disease. 2. Chronic rhinosinusitis with nasal polyps. 3. Refractory chronic cough. 4. Systemic lupus erythematosus. 5. Mechanism of action. 6. Ultra-long-acting. 7. Best in class. 8. Artificial intelligence/machine learning. Deep expertise in inflammatory mechanisms is opening up new opportunities in Respiratory/Immunology Respiratory leadership and deep understanding of inflammation • Nucala (COPD1) • Depemokimab (asthma/CRSwNP2) • Camlipixant (RCC3) Foundation in Immunology • Benlysta (lupus/SLE4) COPD portfolio • New MoAs5 • ULA6 medicines • BIC7 combinations Fibrosis in the lung, liver and kidney Informed by disease, patient and market insights Increased confidence due to genetics, phenotyping, single cell data and AI/ML 8 Next wave…Today…
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19 We have a deep understanding of the multiple pathways driving inflammation in COPD1 Data-driven, genetically validated development Pioneers in establishing role of IL-52 in driving T23 inflammation with Nucala, and in long-acting regimens Advances in understanding of IL-334 and TSLP5 pathways as clinically validated targets for COPD A range of modalities is needed to identify the best possible approach for COPD patients – >300 million people affected globally6 Long-acting combination potential for additive efficacy benefit, reducing exacerbations and keeping people out of hospital 1. Image source: Nature, January 2018. Volume 18. 2. Interleukin-5. 3. Type 2. 4. Interleukin-33. 5. Thymic stromal lymphopoietin. 6. Ruvna L, Sood, A; Clin Chest Med. 2020 Sep;41(3):315-327.
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Odds of COPD are lower in people with genetically reduced IL-33 and TSLP activity (OR, 95% CI)1 Lower IL-33 and TSLP genetic activity is associated with reduced risk of COPD Genetically reduced activity of both TSLP and IL-33 consistent with additive effect Supports differentiated COPD development approach: • Targeting multiple pathways to reach broadest group of patients and deliver increased efficacy 20 1. GSK analyses of UK Biobank data IL-33 and TSLP have strong genetic validation as potential targets in COPD Decreasing risk of COPD OR comparing case vs. control group Expected additive effect
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21 Insights from unique, proprietary data sets support the need for multiple modalities to ensure the right treatment for the right patient Extensive clinical trial data for subgroup insights: • Precision medicine • Interactions with different measures of efficacy of EOS, FEV1, symptom burden Plasma and airway omic analyses for translational insights • MoA vs. endotype • Genetically instrumented combination predictions AI/ML tools for disease progression models • Interpret multi-modal data to build disease progression models Single cell transcriptomics shows differentiated mRNA expression profiles across lung cell types • IL5 axis: epithelial cells • IL33 axis: endothelial cells and mast cells • TSLP axis: dendritic cells Integration with genetics identifies causal cell types Gene expression mechanistic modelling supports opportunity for multiple modalities, complementary to genetic analyses • IL5 and TSLP share downstream signaling cascade • IL33 uses a distinct cascade Sources: Internal analyses using COPD GWAS, COPD ECLIPSE, Human Lung Cell Atlas data sets EOS: Eosinophils. DCs: Dendritic Cells FEV1: Forced expiratory volume 1. MOA: Mechanism of action. AI/ML: Artificial intelligence/machine learning
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22 1. Severe COPD defined as ≥ 2 exacerbations in past 12 months. 2. Vogelmeier et al. Evaluation of exacerbations and blood eosinophils in UK and US COPD populations.Respir Res 20, 178 (2019). 3. Includes Nucala and depemokimab. *Under evaluation. We will expand our COPD leadership exploring a suite of ultra-long-acting medicines to maximise efficacy in the broadest range of patients Severe COPD1 & eos <150 Severe COPD & eos >300Severe COPD & eos 150-300 Long-acting IL-53 Nucala and depemokimab 0 150 300 Eosinophil levels Long-acting TSLP ~ 36% patients 2 ~ 37% patients 2 ~ 27% patients 2 Long-acting IL-33 Long-acting combo TSLP/IL-33*
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23 Ultra-long-acting treatments have the potential to significantly impact outcomes in COPD Need for improved treatment options Benefits of ULA medicines Sustained suppression of inflammation to prevent disease progression New efficacy benchmarks: exacerbation/ hospitalisation reduction Combination potential for broader patient coverage Adherence and patient convenience >40% COPD patients experience exacerbations on triple therapy1 <50% 5-year survival after being hospitalised with COPD exacerbation2 <50% compliance with inhaled therapy3 33% persistence to biologic therapy4 1. Lahousse L, et al. Eur Respir J 2017;50(2):1602470. 2. Sánta B, et al. Pulmonology 2023;29:284–91. 3. Turégano-YedroInt M, et al. J Chron Obstruct Pulmon Dis. 2023 Dec 4;18:2887–2893. 4. GSK data on file: US Claims Data, Compliance & Persistency Dashboard. New-to-Brand. 12M persistency.
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2024 2025 2026 2027 2028 2029+ Nucala COPD Depemokimab COPD LA IL-33 LA TSLP IL-33/TSLP combo* 24 We are well placed to execute new COPD programmes across IL-5, IL-33 and TSLP with phase III starts from 2025 onwards MATINEE phIII read out US approval Phase III Phase IIIPhase I (a/b) Phase IIIPhase II (asthma) Phase II POC Phase III Multiple data read outs and regulatory filings Timeline is illustrative *Under evaluation
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25 1. Global Burden of Disease Study 2017 Cirrhosis collaborators. 2020. 2. Miao et al. Trends in Endocrinology & Metabolism, August 2024, Vol. 35, No. 8. 3. Allen et al. Postgraduate Medicine. 2024, Vol 136, No. 3, 229–245. 4. Younossi et al. Hepatol Commun. 2023 Dec 22;8(1):e0352. 5. CDC. Prevalence of Overweight, Obesity, and Severe Obesity Among Adults Ages 20 and Older: United States, 1960-1962 Through 2017-2018. 6.National Institute on Alcohol Abuse and Alcoholism. September 2024. Our expertise in inflammatory pathways and fibrosis is unlocking new opportunities beyond the lung, for example in liver disease Alcohol-related liver disease (ALD) ~26 million cases of advanced ALD globally1 #1 cause of liver transplant in the US 4 60% of US general population actively drink alcohol and 10% have alcohol dependency 6 No pharmacological treatment options available Metabolic dysfunction-associated steatohepatitis (MASH) 3-5% global prevalence2 <10% patients diagnosed3 #2 cause of liver transplant in the US 4 74% of US general population overweight/obese 5 Sub-optimal current standard of care Steatotic Liver Disease: affects ~5% of general population; major global cause of cirrhosis with significant unmet need1 Metabolic Syndrome Alcohol
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Naturally occurring variants in HSD17B13 are protective against both alcohol and non-alcohol related liver disease ~30-50% risk reduction vs. non carriers2 Protective effect is maintained and potentially enhanced despite continued alcohol consumption, • Suggests potential for efficacy in those at highest risk3 26 1. *Abul-Husn 2018 (PMID 29562163); ** Abul-Husn 2018 (PMID 29562163) & FinnGen & UK Biobank; + Innes 2020 minus UK Biobank (PMID 32561361). 2. Motomura et al. J Pers Med. 2021 Jun 30;11(7):619. 3. Gellert-Kristensen 2019 (PMID 31155741). HSD17B13 has strong genetic validation as a target in SLD HSD17B13 loss of function lowers risk across liver diseases1
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27 1. Mack et al. J Hepatol. 2023 Apr;78(4):684-692. 2. ALT: Alanine aminotransferase. GSK‘990 showed deep and durable reduction in HSD17B13 expression and reductions in key marker of liver injury >40% reduction in liver enzymes associated with liver injury1Deep and durable >90% reduction in HSD17B13 protein1 25mg (n=6) 100mg (n=6) 200mg (n=6) 2
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28 1. Small interfering RNA. 2. Nonalcoholic steatohepatitis/Metabolic dysfunction-associated steatohepatitis. 3. Metabolic alcohol-related liver disease. 4. Alcohol related liver disease. Tech-enabled GSK’990 development programme underway across spectrum of SLD siRNA1 modality could reach previously inaccessible targets Genetically validated targets Single cell sequencing, imaging and patient endophenotyping Biomarker driven to identify right patients and predict treatment outcomes Non-invasive tests with excellent predictive value for clinical outcomes to avoid liver biopsy Oligonucleotide platform Steatotic liver disease (SLD) Phase II STARLIGHT studyPhase IIb HORIZON study NASH/MASH2 MetALD3 ALD4 Tech-enabled SLD programme
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29 Opportunity to develop an SLD1 portfolio of complementary mechanisms to reach a broad group of patients HSD17B13 (GSK’990) Target 1/2 siRNA Target 1/2 siRNA + GSK’990 MASH resolution (% of patients) Fibrosis improvement (% of patients) Two genetically validated targets which complement GSK’990 + oligonucleotide tools against each target to clear fat from liver cells identified by Wave collaboration… Differentiated biology Target regulates toxic saturated fat storage in liver cells Target #1 Genetic association Associated with risk of MASLD2, MASH3, ALD4, liver damage, liver fat and cirrhosis Target #2 Differentiated biology Target promotes accumulation and synthesis of lipid droplets Genetic association Associated with risk of MASH, MASLD, elevated liver enzymes and cirrhosis 1. Steatotic liver disease. 2. Metabolic dysfunction-associated steatotic liver disease. 3. Metabolic dysfunction-associated steatohepatitis. 4. Alcohol related liver disease. …could expand our patient reach with GSK’990 in mono or combo therapies
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30 SEA: severe eosinophilic asthma. CRSwNP: chronic rhinosinusitis with nasal polyps. COPD: chronic obstructive pulmonary disease. HES: hypereosinophilic syndrome. EGPA: Eosinophilic granulomatosis with polyangiitis. PF: pulmonary fibrosis. RCC: refractory chronic cough. SSC-ILD: systemic sclerosis-interstitial lung disease. CTD-ILD: connective tissue disease-interstitial lung disease. NCFB: Non-cystic fibrosis bronchiectasis. HRV: human rhinovirus. A1AD: alpha-1 antitrypsin deficiency. MASH: Metabolic dysfunction-associated steatohepatitis. ALD: alcohol related liver disease. HBV: hepatitis B virus. SLD: steatotic liver disease. Timelines are illustrative. Over the next decade, we expect significant approvals in Respiratory and Immunology Focused in new areas, built on our deep expertise and enabled by tech Launched 2025 2026 2027 2028 2029+ camlipixant RCC TG2 PF Benlysta SSC-ILD Benlysta CTD-ILD Low Carbon Ventolin Asthma PI4Kb HRV LA IL133 COPD LA IL133 NCFB LA IL133 + TSLP Combo COPD LA TSLP Asthma Pi4Kb2 HRV TG2 PF WVE-006 A1AD PoC readouts driving leadership in COPD linerixibat PBC GSK’990 ALD GSK’990 MASH SiRNA bepirovisen Seq therapy HBV PoC readouts driving leadership in liver disease Lung Liver Launch PoM/PoC Launch PoM/PoC LA combo COPD LA TSLP Asthma. CRSwNP, COPD depemokimab COPD LA IL33 COPD, NCFB Nucala SEA, CRSwNP Nucala COPD depemokimab SEA, CRSwNP depemokimab HES, EGPA GSK’990 MASH GSK’990 ALD SiRNA bepirovirsen Seq therapy HBV bepirovirsen HBV
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31 Key takeaways • Strong progress in R&D with 67 pipeline assets including 18 in Phase III • Prioritising investment to accelerate new, high-potential development opportunities in: - Oncology, expanding beyond haematological and gynaecological cancers using ADCs for the treatment of solid tumours - Respiratory and Immunology, building on decades of knowledge in inflammatory mechanisms to target fibrotic lung, liver and kidney disease • Examples of differentiated next-wave pipeline to deliver long-term growth • Multiple data and regulatory catalysts to come and 5 approvals expected in 2025
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32 Q&A Dr Tony Wood Chief Scientific Officer Luke Miels Chief Commercial Officer Dr Hesham Abdullah SVP, Global Oncology R&D Dr Kaivan Khavandi SVP, Global Respiratory/Immunology R&D