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1. Choose the path for rapid and sustained K + Control in CKD : introducing Lokelma ID 6868/Expired Feb 2026

2. DISCLAIMER The meeting and material are organized and sponsored by PT. AstraZeneca Indonesia. This is a promotional meeting. The speaker in this meeting receive honoraria from PT. AstraZeneca Indonesia. Pertemuan ilmiah dan materi dalam pertemuan ini diselenggarakan dan disponsori oleh PT. AstraZeneca Indonesia. Pertemuan ilmiah ini adalah pertemuan yang bersifat promosi. Pembicara dalam pertemuan ilmiah ini menerima honoraria dari PT. AstraZeneca Indonesia . 2

3. Agenda Patient Case 01 Hyperkalemia and unmet need 02 What’s Lokelma 04 Guidelines 03 Lokelma Rapid, Sustained and Well Tolerated 05 Dosage and How to use 06

4. Patient Case 1 A patient with CKD stage 3 and T2D is taking an ACEi . BP is 160/90 mm Hg with persistent proteinuria. The patient is finding it difficult to adhere to a strict diet, resulting in rising potassium levels. The last potassium reading taken was 5.5 mmol/L. What do you do? Refer to a dietician to discuss meal plans Downtitrate ACEi Start treatment with C PS Do nothing and continue to monitor potassium levels Follow-up questions: At what point, if at all, would you consider using a novel potassium binder in this patient? Are there any particular characteristics of LOKELMA that may benefit this patient? Are there any particular considerations when initiating LOKELMA in this patient? e.g. co-administration of drugs and K + monitoring

5. A non-diabetic patient with CKD stage 3 is being treated with an ARB for their hypertension. The patient would benefit from a higher dose of ARB due to their increasing blood pressure, but the patient’s serum potassium level is already at 5.5 mmol /L. What do you do? Increase dose of ARB and increase potassium monitoring Add alternative BP-lowering drug and continue monitoring potassium level Downtitrate ARB Start CPS and schedule follow-up to assess patient adherence Follow-up questions: At what point would you consider using a potassium binder with this patient? Are there any particular characteristics of LOKELMA that may benefit this patient in the event the patient develops hyperkalaemia? Are there any particular considerations when initiating LOKELMA in this patient if the patient become hyperkalaemic ? e.g. co-administration of drugs and K + monitoring Patient Case 2 ARB, angiotensin receptor blocker; BP, blood pressure; CKD, chronic kidney disease; HK, hyperkalaemia; SPS, sodium polystyrene sulphonate

6. Patient Case 3 A patient with heart failure and CKD stage 4 is taking ACEi for the heart failure. ACEi slowed the decline of eGFR, but the patient recently complained of severe muscle weakness. In the emergency department, a serum potassium level of 6.7 mmol /L was recorded. Following acute treatment, what do you do? Discontinue ACEi Reduce dose of ACEi Monitor potassium regularly Do nothing Follow-up questions: At what point could novel potassium binders be used in the management of HK in this patient? Would there be there any particular considerations when initiating LOKELMA in this patient? e.g. co-administration of drugs and K + monitoring

7. K + homeostasis in the human body a Based on presenter’s own observations GI, gastrointestinal; HK, hyperkalaemia 1. Osorio FV, Linas SL. Disorders of Potassium Metabolism. In: Schrier RW (ed.). Atlas of Diseases of the Kidney. Philadelphia, PA, USA: Wiley-Blackwell; 1999; 2. National Institutes of Health https://ods.od.nih.gov/factsheets/Potassium-HealthProfessional/#h6 (Accessed October 2019); 3. World Health Organization. Potassium intake for adults and children, 2012; 4. Allon M. Metabolism of Potassium Disorders. In: Gilbert SJ Weiner DE (eds.). National Kidney Foundation Primer Diseases. 6th edn . Elsevier; 2014:615–646; 5. Stone M, et al. Nutrients 2016;8:444; 6. Hoorn EJ, Zietse R. Kidney Int 2015;88:1230–1232; 7. Rajendran VM, Sandle GI. Compr physiol 2018;8:1513–1536; 8. Sorensen MV, et al. Eur J Physiol 2010;459:645–656 Extracellular fluid 4 ~4 mmol /L Intracellular fluid 4 ~150 mmol /L GI intake: 100 mmol /day 1 Range: 0–400 mmol /day 2,3 Renal excretion: 90‒95 mmol /day 1 Urine reference range: 20–100 mmol /24 h 1–90% filtered load a GI excretion: 5‒10 mmol /day 1 (Up to 40 mmol/day in CKD a ) Aldosterone ~90% of dietary K + is absorbed from the small intestine 5 Feed-forward mechanism 6 K + reabsorption 7,8 K + secretion 7,8 Hyperkalemia and Unmet Needs

8. Collecting duct lumen Aldosterone receptor Na–K ATPase Na + K + Ca 2+ Mg 2+ K + Na + K + e limination in urine Renal impairment, comorbidities and associated treatments can lead to impaired K + excretion 1–3 1. Palmer BF. N Engl J Med 2004;351:585–592 ; 2. Palmer BF, Clegg DJ. Adv Physiol Educ 2016;40:480–490; 3. Noize P, et al. Pharmacoepidemiol Drug Saf 2011;20:747–753; 4. Eleftheriadis T, et al.  Hippokratia  2012;16:294–302 5 Na–K + pump inhibition: 4 β blockers and digoxin Angiotensinogen Angiotensin I Impaired renin release: NSAIDs, β blockers, cyclosporines Impaired aldosterone metabolism: Adrenal disease, heparin or ketoconazole Renin Angiotensin II Aldosterone KIDNEY Aldosterone receptor inhibition: Spironolactone and eplerenone Inhibition of Na + into cells: Na + channel blockers, such as amiloride , trimethoprim and pentamidine ACE Reduced tubular flow: Renal damage ACEi ARBs Hyperkalemia and Unmet Needs Mild HK: 5.1–5.4 mmol/L; moderate-to-severe HK: ≥5.5 mmol/L ACE, angiotensin-converting enzyme; ACEi , angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blockers, ATPase, adenosine triphosphatase; HK, hyperkalaemia; NSAID, nonsteroidal anti-inflammatory drug

9. HK is diagnosed based on serum K + 1. The American Heart Association. Circulation 2005;112:IV-121-IV-125; 2. Einhorn LM, et al. Arch Int Med 2009;169:1156–1162 Moderate HK Severe HK Mild HK 6.0–7.0 > 7.0 5.0–<6.0 K + level (mEq/L) Diagnosis of HK 1,2 HK, hyperkalaemia Hyperkalemia and Unmet Needs

10. Hyperkalemia is increased in patients with CKD a Adjusted for confounders: race, gender, age, Charlson Comorbidity Index, cancer, diabetes, CVD and RAASi treatment within 30 days; b Potassium ≥5.5 mg/ dL CI, confidence interval; CKD, chronic kidney disease; HK, hyperkalaemia; RAASi , renin–angiotensin–aldosterone system inhibitor Einhorn LM, et al. Arch Intern Med 2009;169:1156–1162 Incidence of HK b (≥5.5 mEq /L) (in patients taking RAASi therapy) P <0.0001 Retrospective analysis of a US database of electronic health records (N>200,000) of veterans with at least one inpatient or outpatient serum K + reading in 2005 Adjusted rate per 100 patient months a Odds ratio for K + of ≥5.5 mEq /L (95% CI) 1.00 No CKD (reference point) N=174,935 CKD stage 3 N=57,798 CKD stage 4 N=8351 CKD stage 5 N=4724 2.24 5.91 11.0 Hyperkalemia and Unmet Needs

11. Normal serum K + range 3.5-5.0 mmol/L 2 a Signficant vs. control group; b Control group comprised of individuals without known HF, CKD, DM, CVD, or HTN. CKD = chronic kidney disease; CVD = cardiovascular disease; DM = diabetes mellitus; HF = heart failure; HTN = hypertension; US = United States. 1. Collins AJ et al. Am J Nephrol. 2017;46:213–221 Relationship between serum K + value and mortality over an 18-month period 1 Analysis of electronic medical record data from multiple US integrated health delivery networks of 911,698 patients with ≥ 2 serum K + measurements between 2007 and 2012 1 All-cause mortality was significantly elevated for every 0.1 mmol/L change in serum K + <4.0 mmol/L and ≥5.0 mmol/L 1 Baseline Serum K + Level (mmol/L) Predicted Probability of Mortality HF, CKD, and DM a CKD (stage 3-5) a HF a DM a Control group b 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 Hyperkalemia and Unmet Needs Hyperkalemia is associated with an increased risk of all-cause mortality in cardiorenal patients

12. 7.7 months 5.9 months 4.8 months a A hyperkalemia event was defined as blood K + >5.0 mmol/L not preceded by a prior episode of elevated potassium within the previous month. 1,2 CKD = chronic kidney disease; HF = heart failure. 1. Thomsen RW et al. Nephrol Dial Transplant . 2018;33:1610-1620; 2. Thomsen RW et al. J Am Heart Assoc. 2018;7:e008912. 6.2 months 5.3 months 4.6 months Population-based cohort study linking individual data from hospital, prescription, and laboratory databases in patients from the Danish National Patient Registry in Northern Denmark (population 1.8 million) during 2000–2012 1,2 Hyperkalemia is an ongoing threat in cardiorenal patients 1 st Event 2 nd Event 3 rd Event 4 th Event 27.5 % n=43,397 43.0 % n=18,644 57.1 % n=10,640 64.0 % n=6808 39.0 % n=12,340 43.2 % n=5326 54.3 % n=2891 60.1 % n=1738 Patients with CKD and HF have recurrent hyperkalemia episodes , with successively shorter time between the episodes 1,2 Patients with CKD 1 (N=157,766) Patients with HF 2 (N=31,649) Proportion of Patients With Recurrent Hyperkalemia Events a and Median Time to Event

13. 1. Dunn J et al. Am J Manag Care. 2015;21:S307–S315; 2. SPS Suspension Prescribing Information, CMP Pharma, Inc. March 2018; 3. Zann V et al. Drug Des Devel Ther . 2017;11:2663–2673; 4. Noel JA et al. JAMA Intern Med. 2019;179:1025-1033; 5. Laureati P et al. Nephrol Dial Transplant. 2020;35:1518-1526. Difficult to adhere to Limiting K + -rich foods can cause constipation Contradicts DASH diet; may worsen chronic hypertension Low-K + diet 1 Efficacy depends on residual renal function (until diuresis is present) Increased risk of gout and diabetes depending on choice of diuretic May produce volume contraction, decreased distal nephron flow, worsening of kidney function, and reduced K + excretion depending on choice of diuretic Diuretics 1 Stopping or suboptimal utilization of renal/ cardioprotective RAASi therapy Discontinuation or dose-reduction of RAASi therapy 1 Long-term efficacy has not been evaluated Gastric irritation, anorexia, nausea, vomiting, constipation and occasionally diarrhea may occur High risk of hospitalizations or death due to serious GI AEs a Hard, gritty texture and unpleasant taste may reduce palatability Traditional K + binders eg, SPS 1-5 Traditional hyperkalemia treatment options are associated with limitations a Based on 2 retrospective analyses where primary outcome was a composite of adverse GI events (hospitalization or emergency department visit with intestinal ischemia/thrombosis, GI ulceration/perforation, or resection/ostomy within 30 days of initial SPS prescription in elderly patients 4 and hospitalization or death due to intestinal ischemia or thrombosis, GI ulcers and perforation) in adult patients. 5 AE = adverse event; DASH = Dietary Approaches to Stop Hypertension; GI = gastrointestinal; RAASi = renin-angiotensin-aldosterone system inhibitor; SPS = sodium polystyrene sulfonate. Hyperkalemia and Unmet Needs

14. KDIGO 2022 GUIDELINE FOR DIABETES MANAGEMENT IN CHRONIC KIDNEY DISEASE 1 Adapted from KDIGO Clinical Practice Guideline for diabetes management in chronic kidney disease, 2020. ACEi = angiotensin-converting enzyme inhibitor; AKI = acute kidney injury; ARB = angiotensin receptor blocker; GI = gastrointestinal; NSAIDs = non-steroidal anti-inflammatory drugs; RAAS = renin-angiotensin-aldosterone system. Initiate ACEi or ARB Hyperkalaemia Reduce dose or stop ACEi or ARB as last resort Normokalaemia <30% increase in creatinine Increase dose of ACEi or ARB or continue on maximally tolerated dose >30% increase in creatinine Monitor serum creatinine and potassium (within 2-4 weeks after starting or changing dose) Review concurrent drugs Moderate potassium intake Consider: Diuretics Sodium bicarbonate Potassium binders Review for causes of AKI Correct volume depletion Reassess concomitant medications ( eg , diuretics, NSAIDs) Consider renal artery stenosis Guidelines 1. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. Kidney International (2022) 102 (Suppl 5S), S1–S127

15. *Summary based on the KDIGO 2021 Guideline for Management of Blood Pressure in Chronic Kidney Disease. Please refer to the Guideline for complete recommendations. ACEi = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; BP = blood pressure; CKD = chronic kidney disease; GFR = glomerular filtration rate; RASi = renin-angiotensin system inhibitor. Adults with high BP and CKD should be treated with a target systolic blood pressure of <120 mm Hg, when tolerated, using standardised office BP measurement (Recommendation 3.1.1) 1 RASi ( ACEi or ARB) should be administered using the highest approved dose that is tolerated to achieve the benefits described because the proven benefits were achieved in trials using these doses (Practice Point 3.2.2) 1 Changes in BP, serum creatinine, and serum potassium should be checked within 2-4 weeks of initiation or increase in the dose of a RASi , depending on the current GFR and serum potassium (Practice Point 3.2.3) 1 Hyperkalaemia associated with use of RASi can often be managed by measures to reduce the serum potassium levels rather than decreasing the dose or stopping RASi (Practice Point 3.2.4) 1 Continue ACEi or ARB therapy unless serum creatinine rises by more than 30% within 4 weeks following initiation of treatment or an increase in dose (Practice Point 3.2.5) 1 Individualisation of management, including consideration of the patient’s characteristics, tolerability, and preferences, is crucial 1 Strategies to control chronic hyperkalaemia include dietary potassium restriction; discontinuation of potassium supplements, certain salt substitutes, and hyperkalaemic drugs; adding potassium-wasting diuretics and oral potassium binders 1 In CKD patients receiving RASi who develop hyperkalaemia , the latter can be controlled with newer oral potassium binders in many patients, with the effect that RASi can be continued at the recommended dose 1 KDIGO 2021 GUIDELINE FOR BLOOD PRESSURE MANAGEMENT IN CHRONIC KIDNEY DISEASE* 1 Note - This is not the full list of Practice Points that sit under Recommendation 3.2.3 Guidelines 1. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 Clinical Practice Guideline for Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021;99(3S):S1-S87.

16. LOKELMA Crystal Structure Average Binding-Site Width: 3 Å O = oxygen atom; Si = silicon atom; SZC = sodium zirconium cyclosilicate; Zr = zirconium atom . Stavros F et al.  PLoS One . 2014;9:e114686. Inorganic crystalline potassium binder; not a polymer Exchanges H + and Na + for K + Highly selective for K + ; binding site width and K + ionic diameter are similar Insoluble, highly stable, and does not expand in water Not systemically absorbed What’s Lokelma

17. LOKELMA Binds K + Throughout the GI Tract For illustrative purposes only . GI = gastrointestinal; SZC = sodium zirconium cyclosilicate. Stavros F et al. PLoS One . 2014;9(12):e114686. Based on in vitro data, SZC may begin working immediately in the small intestine to preferentially capture K + K + is exchanged for hydrogen and sodium Exit Large Intestine Small Intestine K + K + K + K + SZC SZC K + K + SZC SZC K + K + K + SZC Ca 2+ Ca 2+ Ca 2+ Ca 2+ Mg 2+ Mg 2 + Mg 2+ K + K + H + Na + H + Na + SZC K + K + K + K + K + K + K + Na + H + K + Na + K + Na + Na + K + H + K + K + K + K + Na + K + H + Mg 2+ K + K + K + H + K + Na + K + K + K + K + K + K + K + K + K + K + K + K + What’s Lokelma

18. Lokelma Mechanism of Action Highly Selective for K + * Unhydrated . SZC = sodium zirconium cyclosilicate. Stavros F et al.  PLoS One . 2014;9:e114686. Due to similar ionic diameters, K + and NH 4 + fit best in SZC pores, which are ~3 Å in size Dehydrated Na + and Ca 2+ ions are too small to interact with the oxygen therefore entering the SZC pore is energetically unfavorable Relative Diameters of Major Cations* K + NH 4 + Na + H 3 O + Ca 2+ Mg 2+ Diameter (Å) Based on in vitro data, SZC may begin working immediately in the small intestine resulting in the early capture of K + SZC preferentially captures for K + in exchange for Na + and H + , even in the presence of Ca 2+ and Mg 2+ No effect on serum Ca 2+ and Mg 2+ concentrations For illustrative purposes only. What’s Lokelma

19. Selected Characteristics of K+ Binders – Traditional vs Novel This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions. 8 ; a Dose differs for patients on haemodialysis- refer to SmPC for more information. 8 ; Traditional Potassium Binder Novel Potassium Binder Calcium polystyrene sulfonate (CPS) LOKELMA Mechanism Nonspecific calcium cation-exchange resin; hypomagnesemia and/or hypercalcemia may occur 1 Selective potassium binding in exchange for sodium and hydrogen 3 Onset Action may be delayed for 1 to 2 days 1 1 hour 3 Dosing 15 - 30 g orally divided 2 to 3 times daily 2   30 g given as retention enema once daily 2 10 g orally 3 times daily for a maximum of 72 hours (starting dose) 3 5 g orally once daily (recommended starting maintenance dose) 3 Longest Duration Studied Prospectively 7 days 5 1 year 3 Site of K + Capture in Lumen of GI Tract Primarily Colon 1 Small and large intestine 3 Adverse events Cases of intestinal necrosis, which may be fatal, and other serious GI adverse events have been reported 2 Hypokalaemia and oedema-related events 3 Drug Interactions Antacids, laxatives, digitalis, sorbitol, lithium, levothyroxine 2 Administer at least 3 hours before or 3 hours after other oral medications 2 Administer at least 2 hours before or 2 hours after oral medications with clinically meaningful gastric pH–dependent bioavailability 3 What’s Lokelma 1. Resonium calcium. Prescribing Information. Sanofi-Aventis Canada. ; 2 Calcium resonium . Summary of product characteristics. Sanofi.;3. Lokelma . Product Information Indonesia. 2023

20. After first dose of LOKELMA 10 g, the mean change in serum K + was -0.2 mmol/L at one hour (95% confidence interval [CI], -0.3 to -0.2; P <0.001 vs baseline). 2 * HARMONIZE (ZS004), a Phase III, multicentre , multiphase, placebo-controlled study in 258 patients with hyperkalaemia . Open-label phase: LOKELMA 10 g, three times daily, administered for 48 hours, at which time patients (n = 237) with normokalaemia (3.5-5.0 mmol/L) were randomised to LOKELMA or placebo once daily, 5 g, 10 g, or 15 g, for 28 days. 2 Primary endpoint: Mean serum K + level with LOKELMA vs placebo on Day 8-29. Eligible patients then continued treatment with LOKELMA 10 g, once daily, which could be titrated to 5 g, or 15 g, in an 11-month, open-label extension study (ZS004E). 1-3 ONE DOSE of LOKELMA significantly reduced serum K + levels at ONE HOUR vs baseline ( P <0.001)* 1,2 Median time to normokalaemia was 2.2 hours (interquartile range 1.0 to 22.3 hours) 2 RAPID REDUCTION SUSTAINED CONTROL GENERALLY WELL TOLERATED RAPID SERUM K + REDUCTION AS EARLY AS ONE HOUR WITH ONE DOSE 1,2 MEAN SERUM K + LEVELS WITH LOKELMA 10 g THREE TIMES DAILY FOR 48 HOURS (N = 258) 2 Adapted from Kosiborod M, et al, 2014. 5.8 5.2 5.0 5.4 5.6 4.6 4.8 4.4 4 8 12 16 20 24 28 32 36 40 44 48 88% OF PATIENTS Time (hours) Key LOKELMA 10 g doses Mean s erum K + (mmol/L) NORMOKALAEMIA (3.5−5.0 mmol/L) achieved normokalaemia at 48 hours 1 Please note that LOKELMA 15 g is not approved for use in patients not on haemodialysis . References: 1. Indonesia Lokelma Prescribing Information 2023. 2. Kosiborod M, Rasmussen HS, Lanvin P, et al. JAMA. 2014;312(21):2223-2233. 3. U.S. National Library of Medicine. Open-label safety & efficacy of ZS (sodium zirconium cyclosilicate) 10 g, QD to extend Study ZS-004 in hyperkalemia. U.S. National Library of Medicine Web site. https://clinicaltrials.gov/ct2/show/study/NCT02107092?term =zs&show_locs=Y#locn. Accessed June, 2021. LOKELMA

21. * <60 mL/min/1.73 m 2 . RAPID REDUCTION SUSTAINED CONTROL GENERALLY WELL TOLERATED LOKELMA consistently reduced serum K + regardless of comorbidities, use of RAAS inhibitor therapy, or baseline K + level 1 MEAN SERUM K + LEVELS AT 0 AND 48 HOURS ACROSS PRESPECIFIED SUBGROUPS [LEFT] AND BASELINE K + LEVEL [RIGHT] 1 PREDICTABLE K + REDUCTION ACROSS PATIENT TYPES 1 All Taking RAAS inhibitor Diabetes mellitus HF CKD eGFR* CKD history ≥6.0 5.5 to <6.0 <5.5 NORMOKALAEMIA (3.5-5.0 mmol/L) NORMOKALAEMIA 6.2 5.4 4.6 5.8 4.2 5.0 6.2 5.4 4.6 5.8 4.2 5.0 Patient subgroups No. of patients Baseline 258 48 hours 251 169 163 179 172 94 92 170 166 180 173 119 115 100 99 39 37 Baseline 48 hours No. of patients Baseline K + level (mmol/L) Mean serum K + (mmol/L) CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; HF = heart failure; RAAS = renin-angiotensin-aldosterone system. 1. Kosiborod M, Rasmussen HS, Lanvin P, et al. JAMA. 2014;312(21):2223-2233. . LOKELMA

22. Please note that LOKELMA 15 g, is not approved for use in patients not on haemodialysis . References: 1. Indonesia Lokelma Prescribing Information 2023 2. Kosiborod M, Rasmussen HS, Lanvin P, et al. JAMA. 2014;312(21):2223-2233. supplement RAPID REDUCTION SUSTAINED CONTROL GENERALLY WELL TOLERATED SUSTAINED K + CONTROL FOR UP TO ONE YEAR 1,2 88% OF PATIENTS receiving LOKELMA maintained an average serum K + of <5.1 mmol/L over 11 MONTHS 1,2 No dietary restrictions were imposed ; patients were instructed to continue their usual diet without any specified alterations 1 5.8 6.0 5.2 5.0 5.4 5.6 4.6 4.4 4.2 4.8 4.0 8 16 24 32 40 48 1 8 12 15 19 22 26 29 1 57 169 252 337 EXIT EOS Correction (hours) (N = 258) Maintenance fixed dose (day) (N = 237) Maintenance titrated dose (day) (N = 123) NORMOKALAEMIA (3.5–5.0 mmol/L) 1 1 months Mean serum K + (mmol/L) Serum K + levels reverted towards baseline after LOKELMA was discontinued MEAN SERUM K + LEVELS ACROSS CORRECTION AND MAINTENANCE PHASES 1,2 Placebo (N = 85) LOKELMA, 5 g (N = 45) LOKELMA, 10 g (N = 51) Titrated dose EXIT EOS Last visit within 1 day of last dose End of study (7 days ±1 day after last dose) Key LOKELMA

23. Majority of Patients Continued RAASi Therapy While Taking LOKELMA for Hyperkalemia Of the 483 patients who received RAASi therapy at the start of CP: 74% 13% b Maintained same RAASi dose Discontinued RAASi therapy Decreased RAASi dose 87% of patients continued RAASi use while taking SZC ZS-005 ( Phase III) 1 Increased RAASi dose Of the 589 patients who initiated SZC while on RAASi therapy: OPTIMIZE I (Real-world Evidence) 2 83% of patients had new or refilled RAASi prescription following SZC initiation 2 17% 14% b 11% 5% 8% 70% Reference : RAASi = renin-angiotensin-aldosterone system inhibitor ; SZC = sodium zirconium cyclosilicate. 1. Spinowitz BS et al. Clin J Am Soc Nephrol. 2019;14(6):798-809; 2 Agiro A et al. Adv Ther (2023) 40:2886–2901; LOKELMA

24. In studies involving MORE THAN 1,700 PATIENTS , LOKELMA was generally well tolerated, with few adverse reactions and limited drug-drug interactions 1 *Including fluid overload, fluid retention, generalised oedema, hypervolaemia , localised oedema, oedema, oedema peripheral, and peripheral swelling. 1 1. Indonesia Lokelma Prescribing Information 2023 RAPID REDUCTION SUSTAINED CONTROL GENERALLY WELL TOLERATED 5.7% of patients receiving LOKELMA reported oedema-related events,* observed more frequently in patients taking a 15 g dose. No clinically significant changes in urinary sodium excretion, or serum magnesium and calcium levels, were observed with LOKELMA 1 4.1% of patients receiving LOKELMA developed hypokalaemia (serum K + level <3.5 mmol/L), which resolved with dosage adjustment or discontinuation of LOKELMA 1 GENERALLY WELL-TOLERATED K + CONTROL IN CLINICAL TRIALS 1 LOKELMA Disclaimer : Indonesia, the maximal approved dose of Lokelma for maintenance in non-dialysis patient is 10 g

25. ZS-004 (HARMONIZE) : Risk of edema and hypokalemia usually occurred with higher maintenance dose LOKELMA Adverse Events Occurring in ≥5% of Patients, n (%) Correction Phase Correction Phase Maintenance Phase LOKELMA 10 g TID (n=258) LOKELMA 10 g TID (n=258) Placebo QD (n=85) LOKELMA 5 g QD (n=45) LOKELMA 5 g QD (n=45) LOKELMA 10 g QD (n=51) LOKELMA 10 g QD (n=51) LOKELMA 15 g QD (n=56) LOKELMA 15 g QD (n=56) Any event 20 (7.8) 20 (7.8) 27 (31.8) 24 (53.3) 24 (53.3) 15 (29.4) 15 (29.4) 25 (44.6) 25 (44.6) Blood and lymphatic system disorders Anemia 3 (5.4) Gastrointestinal disorders Constipation 2 (0.8) 6 (7.1) 1 (2.0) 1 (1.8) General disorders and administration-site conditions Edema † 2 (2.4) 1 (2.2) 3 (5.9) 8 (14.3) Metabolism and nutrition disorders Hypokalemia (<3.5 mmol/L) 5 (9.8) 6 (10.7) Hypokalemia (reported as AE) 1 (1.8) Infections and infestations Nasopharyngitis 1 (1.2) 3 (5.4) Upper respiratory tract infection 1 (0.4) 1 (1.2) 3 (6.7) 1 (2.0) 1 (1.8) No clinically relevant changes in serum electrolytes (Na + , Mg 2+ , or Ca 2+ ), vital signs, blood pressure, heart rate, or body weight No dose-dependent increase in urinary sodium excretion AE = adverse event; SZC = sodium zirconium cyclosilicate. 1. Kosiborod M et al.  JAMA . 2014;312:2223-2233. LOKELMA Disclaimer : Indonesia, the maximal approved dose of Lokelma for maintenance in non-dialysis patient is 10 g

26. ▶ LOKELMA is a daily maintenance treatment option for hyperkalaemia 1 ▶ Recommended dosing of LOKELMA to achieve and sustain normokalaemia 1 : Maintenance phase Dosing for Non Dialysis vs Dialysis patients 1 It is recommended to monitor serum K+ weekly while the dose is adjusted. To maintain normokalaemia, it is recommended to monitor serum K+ regularly (e.g. monthly or more frequently based on clinical judgement). *If normokalaemia is not achieved within 48 hours of treatment, the same regimen can be continued for an additional 24 hours. If normokalaemia is not achieved after 72 hours of treatment, other treatment approaches should be considered.†Patients who miss a dose should be instructed to take the next usual dose at their normal time. 1. Indonesia Lokelma Prescibingn Information 2023 Correction phase Maintenance phase 3x /day* † 10 g for 24 to 48 hours until normokalaemia is achieved* † 1x /day † 5 g for up to one year ▶ To establish minimum effective dose, LOKELMA may be titrated: Up to 10 g once daily or Down to 5 g once every other day ▶ No more than 10 g once daily should be used for maintenance therapy Maintenance phase /non- dialysis days 1x 5 g ▶ To establish normokalaemia, the dose may be titrated up or down weekly based on the pre-dialysis serum K + after the long interdialytic interval ▶ The dose could be adjusted at intervals of one week in increments of 5 g: Up to 15 g once daily on non-dialysis days Non Dialysis Dialysis Note : in Indonesia, Lokelma only available in 5 g doses Dose and How to use

27. LOKELMA is a powder for oral suspension, available in 5 g dose 1 Mix LOKELMA with 45 mL of water for oral administration 1 Please see limited drug-drug interactions for the types of drugs that cannot be co-administered with LOKELMA. * LOKELMA should be administered at least 2 hours before or 2 hours after oral medications with clinically meaningful gastric pH-dependent bioavailability. LOKELMA can be taken without spacing of dosing times with oral medications that do not exhibit pH-dependent bioavailablity .   Reference: 1. Indonesia Lokelma Prescribing Information 2023. 2. Stavros F, Yang A, Leon A, Nuttall M, Rasmussen HS. PLoS One. 2014;9:e114686. Tasteless and odourless 1,2 May be taken with many other medications and with or without food* 1 No special conditions for storage 1 Ensure patients stir well and drink suspension straight away while still cloudy (powder will not dissolve). Remind patients, if powder settles, to stir again before finishing the drink. 1 ORAL ADMINISTRATION Dose and How to use

28. Summary In cardiorenal patients: HK is an ongoing threat 1,2 Hyperkalemia is associated with an increased risk of all-cause mortality in cardiorenal patients 3 Guidelines recommend RAASi for patients with CKD 4,5 Treat HK to enable patients to remain on optimized RAASi Discontinue RAASi as last resort Treatment with LOKELMA : Rapid and sustained K + reduction for up to 1 year across all patients subgroups, including those on RAASi therapy 6 Enabled patients to continue RAASi dosing 7,8 Generally, well tolerated 9 No restricted K diet 6 . Thomsen RW et al. Nephrol Dial Transplant . 2018;33:1610-1620; 2. Thomsen RW et al. J Am Heart Assoc. 2018;7:e008912. 3. Collins AJ et al. Am J Nephrol. 2017;46:213–221; 4. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. Kidney International (2022) 102 (Suppl 5S), S1–S127. 5. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 Clinical Practice Guideline for Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021;99(3S):S1-S87. 6. Kosiborod M, Rasmussen HS, Lanvin P, et al. JAMA. 2014;312(21):2223-2233. 6. Kosiborod M, Rasmussen HS, Lanvin P, et al. JAMA. 2014;312(21):2223-2233. 7. Spinowitz BS et al. Clin J Am Soc Nephrol. 2019;14(6):798-809; 8 Agiro A et al. Adv Ther (2023) 40:2886–2901; 9. Indonesia Lokelma Prescribing Information 2023

29. ABBREVIATED PRESCRIBING INFORMATION LOKELMA® (Sodium Zirconium Cyclosilicate), Powder for Oral Suspension 5 g & 10 g. Each sachet contains sodium zirconium cyclosilicate equivalent to sodium. PRESENTATION: LOKELMA (Sodium Zirconium Cyclosilicate) Powder for oral suspension. White to grey powder. INDICATION: Lokelma is indicated for the treatment of hyperkalemia in adult patients. Lokelma should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action DOSAGE: Correction phase : The recommended starting dose of Lokelma is 10 g, administered three times a day orally as a suspension in water. When normokalaemia is achieved, the maintenance regimen should be followed. Typically, normokalaemia is achieved within 24 to 48 hours. If patients are still hyperkalaemic after 48 hours of treatment, the same regimen can be continued for an additional 24 hours. If normokalaemia is not achieved after 72 hours of treatment, other treatment approaches should be considered. Maintenance phase : When normokalaemia has been achieved, the minimal effective dose of Lokelma to prevent recurrence of hyperkalaemia should be established. A starting dose of 5 g once daily is recommended, with possible titration up to 10 g once daily, or down to 5 g once every other day, as needed, to maintain a normal potassium level. No more than 10 g once daily should be used for maintenance therapy. Serum potassium levels should be monitored regularly during treatment. Monitoring frequency will depend upon a variety of factors including other medications, progression of chronic kidney disease and dietary potassium intake. If severe hypokalaemia should occur, Lokelma should be discontinued and the patient re-evaluated. Patients on chronic haemodialysis : For patients on dialysis Lokelma should only be dosed on non-dialysis days. The recommended starting dose is 5 g once daily. To establish normokalaemia (4.0-5.0 mmol/L), the dose may be titrated up or down weekly based on the pre-dialysis serum potassium value after the long inter-dialytic interval (LIDI). The dose could be adjusted at intervals of one week in increments of 5 g up to 15 g once daily on nondialysis days. It is recommended to monitor serum potassium weekly while the dose is adjusted; once normokalaemia is established, potassium should be monitored regularly (e.g., monthly, or more frequently based on clinical judgement including changes in dietary potassium or medication affecting serum potassium). METHOD OF ADMINISTRATION For oral use. The suspension can be taken with or without food. CONTRAINDICATION: hypersensitivity to the active substance(s). WARNINGS AND PRECAUTIONS: Serum potassium levels : Serum potassium should be monitored when clinically indicated, including after changes are made to medicinal products that affect the serum potassium concentration and after the Lokelma dose is titrated. Hypokalaemia : Dose titration as described under maintenance posology may be required in such cases to prevent moderate to severe hypokalaemia . In patients with severe hypokalaemia , Lokelma should be discontinued and the patient re-evaluated QT Prolongation : During correction of hyperkalaemia , a lengthening of the QT interval can be observed as the physiologic result of a decline in serum potassium concentration. The risk of interaction with X-rays : Sodium zirconium cyclosilicate may be opaque to X-rays. If the patient is having abdominal X-rays, radiographers should keep this in mind. Intestinal perforation : The risk for intestinal perforation with the use of Lokelma is currently unknown. Sodium content : Lokelma is considered high in sodium. This should be particularly taken into account for those on a low salt diet ID-6161 Expiration Date: 13/09/2025 INTERACTIONS: As sodium zirconium cyclosilicate is not absorbed or metabolised by the body, and does not meaningfully bind other medicinal products, there are limited effects on other medicinal products. Sodium zirconium cyclosilicate can transiently increase gastric pH by absorbing hydrogen ions and can lead to changes in solubility and absorption kinetics for co-administered medicinal products with pHdependent bioavailability UNDESIRABLE EFFECTS: (≥ 1/100 to < 1/10) : Hypokalaemia , oedema related event. Pack size Lokelma 5 g, Box, 30 Sachets: Reg. No: DKI2327900623A1 Lokelma 10 g, Box, 30 Sachets: Reg. No: DKI2327900623B1 HARUS DENGAN RESEP DOKTER Further information is available on request from PT AstraZeneca Indonesia Perkantoran Hijau Arkadia Tower G, 16th fl , Jl. T.B. Simatupang Kav . 88, Jakarta – 12520 Tel: [phone] LOKELMA is a trademark of AstraZeneca group of companies. © AstraZeneca 2023. PromomatsID :ID-6161 Date of preparation : 09 September 2023 Date of Expiry : 09 September 2025 Based on Doc ID : Doc ID-005028566 (approval 31st March 2023) LOKELMA Abbreviated Prescribing Information