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Developing new therapies to treat inflammatory causes of kidney disease with unmet clinical needs Investor Presentation August 2025 Authorised for lodgement by the Board of the Company For personal use only
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Forward looking statements This presentation includes forward-looking statements that are subject to risks and uncertainties. Although we believe that the expectations reflected in the forward looking statements are reasonable at this time, Dimerix can give no assurance that these expectations will prove to be correct. Readers are cautioned not to place undue reliance on forward-looking statements. Actual results could differ materially from those anticipated. Reasons may include risks associated with drug development and manufacture, risks inherent in the regulatory processes, delays in clinical trials, results of clinical trials, contractual risks, risks associated with patent protection, future capital needs or other general risks or factors, along with those factors outlined in the most recent Dimerix Limited Annual Report. For personal use only
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Overview Phase 3 Global Opportunity 1. Guruswamy Sangameswaran KD, Baradhi KM. Focal Segmental Glomerulosclerosis (July 2021), online: https://www.ncbi.nlm.nih.gov/books/NBK532272/; 2. ASX releases: 14Dec15, 21Nov18, 07Jun21; 3. ASX release 05 October 2023, 27 May 2024, 07 January 2025 and 01 May 2025 FSGS indication a rare disease that causes scar tissue of kidneys, which leads to irreversible kidney damage1 No approved treatments available to treat FSGS: damage can lead to dialysis, transplant or death1 Orphan drug designation regulatory, marketing exclusivity and pricing benefits in key territories2 4 DMX-200 licensing partners across key territories3 >$65 million in total payments received to date1 ~$1.4 billion in total upfront & potential development and sales milestone payments plus royalties3 Lead drug candidate DMX-200 in a Phase 3 clinical trial for focal segmental glomerulosclerosis (FSGS) DMX-200 (QYTOVRA® in some territories) For personal use only
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Mechanism of Action Precision therapy to disrupt inflammatory feedback loops in the kidney of patients with FSGS1 Pre-clinical FDA confirmed proposed pre-clinical safety package sufficient to support marketing submission2 Manufacturing Commercial scale up in place – manufacturing sites in USA3 Phase 1 / Phase 2 clinical trials Encouraging efficacy and positive safety signals across Phase 1 & Phase 2 studies (n=>100), including demonstrating a reduction in proteinuria and inflammatory markers in FSGS patients4 ACTION3 Phase 3: Part 1 interim analysis Interim analysis (n=72 @ 35 weeks) showed DMX-200 performing better than placebo in reducing proteinuria5 FDA and Project PARASOL Alignment on proteinuria as primary endpoint for final approval6 3rd Party Validation 4 licensing deals executed for various key territories, all of whom conducted independent, extensive due diligence7 ACTION3 Phase 3: Part 2 interim analysis Blinded data collection and analysis expected after PARASOL project outcomes and FDA feedback6 ACTION3 Phase 3: Part 3 final analysis 2-year proteinuria (potential primary endpoint) and eGFR (primary and/or secondary endpoint) data serves as basis for full approval (n=~286) 1. Ayoub MA, et al. (2015) PLoS One; doi.org/10:e0119803; 2. ASX release 25 November 2019; 3. ASX investor presentation 09Mar20; 4. Repeated measures mixed model analysis; top line data was reported as grouped analysis on 29 July 2020, study not designed for statistical significance; 5. Predictive Power statistical model, using industry standard as set by the independent renal biostatistician consultant for Dimerix, . Interim Phase 3 analysis data does not gua rantee a statistically significant outcome at the end of the trial, ASX release 11 March 2024; 6. FDA Meeting Outcomes, ASX release 28 April 2025, n=approx. 144; 7. ASX release 05 October 2023, 27 May 2024, 07 January 2025 and 01 May 2025 For personal use only
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Cycle of damage : in glomerular diseases What is FSGS? Focal = some Segmental = sections Glomerulo = of the kidney filtering units Sclerosis = are scarred 3 Fibrosis causes loss of kidney cells (cannot regenerate) 2 Constant pressure causes inflammation of kidney cells: subsequent scarring/fibrosis 1 High blood pressure causes hyperfiltration within blood vessels of the kidney1 Less kidney cells cause further hyperfiltration and inflammation As cells die, kidney becomes more “leaky”, and protein spills into the urine (proteinuria) Kidney vessels have to work harder under high pressure 1. For personal use only
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1. Cycle of damage : in glomerular diseases This synergistic activity of both agents disrupts the cycle of damage in FSGS What is FSGS? Focal = some Segmental = sections Glomerulo = of the kidney filtering units Sclerosis = are scarred 3 Fibrosis causes loss of kidney cells (cannot regenerate) 2 Constant pressure causes inflammation of kidney cells: subsequent scarring/fibrosis 1 High blood pressure causes hyperfiltration within blood vessels of the kidney1 targets step 1: angiotensin receptor blocker (ARB) lowers blood pressure1 interrupts step 2 - the inflammatory pathway to target decreasing inflammation DMX-200 Existing blood pressure medication For personal use only
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DMX-200: mechanism of action Podocyte preservation1 Sham Vehicle DMX-200 ARB DMX-200 +ARB Podocytes, n/gcs 20 15 10 5 0 * * * † Sham Vehicle DMX-200 ARB DMX-200 +ARB Macrophages, n/area 200 150 100 50 0 * † † †§ Macrophage infiltration1 uMCR = Urinary MCP-1 creatine ratio; PCR = protein creatinine ratio; *placebo adjusted difference; 1. Ayoub MA, et al. (2015) PLoS One; doi.org/10:e0119803; 2. ASX presentation 27 October 2020; 3. Liu Y. et al (2024) Role of MCP-1 as an inflammatory biomarker in nephropathy, Front. Immunol., Sec. Inflammation doi.org/10.3389/fimmu.2023.13030762.4. De Vriese, AS, et al. (2021) Nat Rev Nephrol (2021). https://doi.org/10.1038/s41581 -021-00427-1; 2. MCP-1 regulation2 • CCR2 is required for recruitment of inflammatory cells to the kidney • Macrophage/monocyte: regulate inflammatory cells • Podocytes: specialist filtration cells in the kidney DMX-200 blocks CCR21 DMX-200 preserves podocytes1 DMX-200 reduces inflammatory cells1,2,3 Healthy podocyte4 -100% -50% 0% 50% 0 8 16 uMCR normalised Weeks On active On placebo -37%* -39%* Damaged podocyte4 For personal use only
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Measuring kidney damage – surrogate endpoints 1. National Kidney Foundation: Estimated Glomerular Filtration Rate (eGFR): https://www.kidney.org/atoz/content/gfr; 2.Gurusw amy Sangameswaran KD, Baradhi KM. Focal Segmental Glomerulosclerosis (July 2021), online: https://www.ncbi.nlm.nih.gov/books/NBK532272/; 3. Nephcure FSGS living with the disease (2024) at https://nephcure.org/livingwithkidneydisease/ns-and-other-glomerular-diseases/understanding-fsgs/ 2. Proteinuria • A healthy kidney is a good filter and allows little to no protein in the urine2 • When kidneys are damaged, protein can leak into the urine causing proteinuria • Proteinuria represents an important early marker of kidney function3 Inside a healthy kidney Inside a damaged kidney Treatments, such as DMX-200, aim to bring the FSGS slope back up: • can add years to the life of the kidney • potential to delay dialysis and/or kidney transplant 1. Estimated glomerular filtration rate (eGFR) • Kidney function can be measured using eGFR: o how many millilitres of blood is filtered by the kidney per minute • eGFR slope naturally declines as we age1 • In FSGS patients, it is crashing For personal use only
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“Any reduction in proteinuria could yield years of preserved native kidney function and delay the onset of kidney failure and its attendant morbidity and mortality” Kidney survival study – Troost et al, August 20203 DMX-200: Phase 2 met primary and secondary endpoints PCR = protein creatinine ratio; ARB = angiotensin receptor blocker; 1. Repeated measures mixed model analysis; top line data was reported as grouped analysis on 29 July 2020, study not designed for statistical significance; 2. Trachtman, et al., 2018. J Amer Soc Nephrology 29(11):2745 -2754; 3. Troost JP et al (August 2020); doi.org/10.1053/j.ajkd.2020.04.014 Clinically meaningful outcomes achieved for patients,2,3 with no safety issues E F F I C A C Y • 86% of patients demonstrated reduced proteinuria • DMX-200 reduced inflammatory biomarker by 39% vs placebo S A F E T Y • No safety concerns – reduced development risk Average reduction of 17% in proteinuria after 16 weeks treatment on DMX-200 versus placebo1 For personal use only
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phase 3 clinical trial 1. ASX release 30 Dec 2024; 2. As at 16 Aug 2025, including 223 adults and 2 paediatric patients; 3. Interim Phase 3 analysis data does not guarantee a statistically significant outcome at the end of the trial, ASX release 11 March 2024; 4. The potential for accelerated (or conditional) approval submissions, following the second interim analysis and any required u nblinding, will be assessed based on outcomes from PARASOL analysis, recommendations of the IDMC and discussions with the appropriate regulatory authorities such as the FDA in the US; 5. Regardless of any accelerated (conditional) approval potential, ACTION3 study will complete full 2 year analysis and regulatory submission for potential traditional (full) approval; uPCR = urinary proteinuria; eGFR = estimated glomerular filtration rate (kidney function); A randomised, double-blind, multi-centre, placebo-controlled study of renal outcomes of DMX-200 in patients with FSGS receiving an ARB Potential to submit for conditional marketing approval, subject to FDA discussion 3 ARB + DMX-200 ARB + placebo Part 2: analysis outcome4 Total of 286 patients @ 104 weeks (uPCR/eGFR)5 Phase 3 Trial Timeline Part 3: final analysis Background • Patients recruited, then screened and stabilised on background medications • Patients randomised to receive drug or placebo • DXB remains blinded at all times during study 72 patients @ 35 weeks Successful analysis outcome3 (using statistical measure) (% change in uPCR) Open Label Extension DMX-200 ACTION3 Study End blinded interim data collection and analysis following additional analysis of the PARASOL data and FDA feedback4 ~286 Total number of patients required - anticipated H2 20251 225 Patients recruited, randomised and dosed2 54 Patients enrolled over into open label extension study2 For personal use only
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1. PLoS Clin Trials. 2007 Apr 13;2(4):e18. doi: 10.1371/journal.pctr.0020018; 2. Coalition made up of: NephCure, ISGD, NKF, KHI are co -sponsors of the project, FDA and EMA involvement, University of Michigan is data coordinating center, Industry invited as participants; eGFR : Estimated Glomerular Filtration Rate Project PARASOL – an FDA-led working group Project PARASOL: 24-month data analysis ➢ PARASOL formed to address the need to validate alternative surrogate endpoints for FSGS ➢ Coalition of nonprofit organisations, academia, registries, trials and Sponsors2 • PARASOL confirmed: eGFR slope is a valid endpoint for predicting progression of kidney disease • PARASOL demonstrated proteinuria is a valid endpoint for predicting progression of kidney disease • FDA confirmed: a reduction in proteinuria is a validated endpoint for DMX-200 for full marketing approval for FSGS at 24-months 1 DIMERIX & PARASOL project: earlier data point analysis ➢ Initial analysis conducted primarily on available 24-month data ➢ Initial analysis conducted on population similar, but not identical, to ACTION3 • Analysis of PARASOL population overlaid on ACTION3 population required • Relationship between earlier time points, such as 12- month, and 24-month data required • Assuming strong correlation to risk of kidney failure identified at 12-months, seek FDA alignment for accelerated approval 2 Working groups not uncommon to review and recommend potential endpoints for indications without any approved therapies as new information comes to light, for example, results from other trials or identification of better biomarkers or surrogate outcome measures1 For personal use only
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Interim analysis process Step 1 Receive PARASOL FSGS working group 12-month data analysis1 Step 2 Seek FDA alignment on interim endpoints for accelerated approval and interim powering1 Step 3 Blinded statistical powering interim analysis outcome and update ACTION3 clinical study protocol1,2 Step 4 Final decision on submission for accelerated approval1,2 In line with best practice, endpoints must be set prior to any potential unblinding of data, to maintain integrity of the study 1-3 months ~1 month3~3 months3 1. ASX release 28 April 2025; 2. The potential for unblinding and accelerated (or conditional) approval submissions, followin g the second interim analysis, will be assessed based on outcomes from PARASOL analysis, recommendations of the IDMC and agreement with the appropriate regulatory authorities such as the FDA in the US; 3. Timing su bject to PARASOL outcome, FDA feedback and regulatory acceptance in each territory Positive Type C meeting held in March 2025 with US Food & Drug Administration (FDA) on proteinuria trial endpoints for full approval, and potential for accelerated approval for DMX-2001 Assuming strong correlation to risk of kidney failure identified Assuming FDA aligned with mid- trial endpoints Timing subject to regulatory acceptance of the protocol in each territory From today: For personal use only
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Aligning global regulatory pathways USA EU Japan Current primary endpoints for traditional approval for FSGS Proteinuria or eGFR eGFR eGFR Faster access to market if interim endpoint agreed by regulators 1 Yes Accelerated Approval program Yes Conditional Marketing Authorisation Yes Sakigake program 1. Franco, P., Jain, R., Rosenkrands-Lange, E. et al. Regulatory Pathways Supporting Expedited Drug Development and Approval in ICH Member Countries. Ther Innov Regul Sci 57, 484–514 (2023). https://doi.org/10.1007/s43441-022-00480-3; 2. There is no guarantee that territories will accept DMX -200 for accelerated/conditional approval in FSGS To accelerate patient access to much needed treatment in areas of serious and life-threatening diseases and unmet medical need, many regulatory authorities have put in place regulatory pathways to expedite drug development and approval1,2 For personal use only
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Competitive landscape in FSGS Phase 1 Phase 2 Phase 3 Company DMX-200 Sparsentan Travere Therapeutics VX-147 Vertex Pharmaceuticals BI-764198 Boehringer Ingelheim Atrasentan Chinook R3R01 River 3 Renal Sources: Company Documents, Statutory and Regulatory Filings APOL1 inhibitor – specific type of genetic FSGS TRPC inhibitor AT1R / ETA antagonist Lipid modifying Inflammatory modulator No approved therapies for FSGS Low competition DMX-200 is the only inflammatory modulator in development AT1R/ETAR dual inhibitor – Failed Phase 3 eGFR endpoint: resubmitted to FDA on proteinuria endpoints For personal use only
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FSGS market – potential for growth >200,000 ~ 57,400 ~ 50,071 ~7,329 Estimated global incidence of FSGS/year4 Estimated incidence of FSGS/year across unlicensed territories4 Estimated incidence of FSGS/year across all Dimerix licensed territories4 Global prevalence FSGS patients 3 ➢ Prevalence refers to the total number of existing cases (new and old) ➢ Incidence refers to the number of new cases of a disease within a specified time period Global incidence rate of FSGS per capita per year1 7 per 1,000,000 FSGS is the most frequent primary glomerular disease that reaches end-stage renal failure in the US2 FSGS diagnosis driven by rates of biopsy - growth potential as biopsy rates increase Biopsy For personal use only
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1. US Medicare Drug Price Negotiation Program: https://www.cms.gov/priorities/medicare -prescription-drug-affordability/overview/medicare-drug-price-negotiation-program/guidance-and-policy-documents; 2. ASX investor presentation 09 March 2020; 3 https://www.reuters.com/business/healthcare -pharmaceuticals/us-fda-approves-travere-therapeutics-kidney-disorder-drug-2023-02-17/; 4. http://www.vanrafia.com; 5. Ito, et al., 2025. https://doi.org/10.1182/blood.2024025176; 6. https://endpts.com/fda-clears-traveres-rare-kidney-disease-drug-will-come-with-rems-program; 7. https://www.calliditas.se/en/ wp-content/uploads/sites/2/2018/01/fda-approval-webcast- presentation.pdf; 8. Kanavos, P et al. (2018) Pharmaceutical pricing and reimbursement in the Middle East and North Africa re gion; 9. J Mark Access Health Policy. 2016 Mar 15;4:10.3402/jmahp.v4.30458. doi: 10.3402/jmahp.v4.30458 Example ex-US pricing for other rare kidney disease drugs: in the US (i.e. Filspari in IgAN)6 : US$9,900 p/month in Europe/UK (i.e. Kinpeygo/Tarpeyo)7 : US$8,267 p/month Other key territories, including Middle East and China, use US and/or Europe as pricing reference8.9 DMX-200 Commercial manufacturing sites established in USA3 US Medicare Drug Price Negotiation Program1 US Medicare Drug Price Negotiation Program exempts orphan drugs that treat “only one rare disease or condition’’ from drug price negotiations 0 100,000 200,000 300,000 400,000 500,000 600,000 Filspari Tarpeyo Astrasentan Fabhalta $USD/annum USA retail price for IgAN products 53 3 4 For personal use only
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A partner that has existing/proven infrastructure to deliver DMX-200 to as many FSGS patients in need of treatment A partner that recognises the overall value of the asset and views it as a strategic priority A partner with a collaborative approach who will work almost as an extension of the Dimerix team to achieve the best outcome for the product and the patient 4 exceptional, high quality partners, exponentially increasing collective knowledge & expertise, providing strong support in advancing & commercialising DMX-200 as a potential new treatment for FSGS For personal use only
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Summary of licensing deals for DMX-200 to date 1. ASX release 01 May 2025; 2. Based on Euro conversions & further terms outlined in ASX Announcement on 5 October 2023; 3. B ased on US dollar conversions & further terms outlined in ASX Announcement on 27 May 2024; 4. Based on Japanese ¥ Yen conversions & further terms outlined in ASX Announcem ent on 7 January 2025 Licensing deals collectively valued up to ~AU$1.4 billion in total upfront and potential milestone fees plus royalties1 Dimerix has successfully partnered DMX-200 across key markets United States AU$48m1 Upfront Up to AU$892 million1 Milestones Escalating low- teen-low twenties% Royalties EU, CA, AU, NZ AU$10.8m2 Upfront Up to AU$219 million2 Milestones Escalating mid-teen-20% Royalties GCC, Iraq AU$0.5 million3 Upfront Up to AU$120 million3 Milestones Starting at 30% Royalties Japan AU$7.2 million4 Upfront + 1st milestone Up to AU$100 million4 Milestones Between 15- 20% Royalties 1 2 3 4 Over AU$65 million in total payments received For personal use only
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Potential for additional partnering opportunities Significant potential additional global deal value remains, as Dimerix pursues and progresses licensing opportunities with potential partners outside the licensed territories, including in Mainland China For personal use only
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Corporate overview 1. As at 15 August 2025; 2. Past 30 trading days liquidity as at 18 August 2025; 3. Shareholder register as at 15 August 2025 Ticker Symbol ASX: DXB Cash Balance (Jun25) $68.3 million Market Capitalisation1 $282 million Share price1 $0.47 Total ordinary shares on issue1 600,184,606 Average Daily Liquidity by value for past 30 trading days2 $1.12 million S H A R E P R I C E S U B S T A N T I A L S H A R E H O L D E R S 3 Position Holder Name Holding % IC 1 Mr P Meurs 87,259,311 14.5% TOTAL (TOP 5) Shareholders 144,974,173 24.2% For personal use only
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Potential catalysts CY 2025 DMX-200 licensed in US for up to ~AU$940 million1 DMX-200 licensed in Japan for up to ~AU$107 million2 3 First development milestone received from FUSO of AU$4.1 million 4 ➢ Outcome of PARASOL working group analysis anticipated Q3 20255 ➢ FDA feedback anticipated Q4 20255 ➢ Blinded interim data collection anticipated in Q4 20253 • Potential for accelerated (or conditional) approval submission, subject to PARASOL outcomes, FDA feedback and interim analysis outcomes3,6 ➢ Full study recruitment of 286 adult patients anticipated in H2 20256 ➢ Additional pipeline opportunity(s) identified ➢ Additional licensing partners for DMX- 200: Dimerix continues to pursue potential licensing opportunities in un- licensed territories, including China ➢ Additional development milestone payments from existing licensees if milestone achieved 1. ASX release 01 May 2025; 2. ASX release 07 January 2025 3. FDA Meeting Outcomes, ASX release 28 April 2025; 4. ASX release 30 June 2025; 5. ASX Presentation 07 August 2025; 6. ASX release 30 December 2024 Q1/Q2 2025 1 Potential upside 3 Q3/Q4 2025 2 For personal use only
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W E L L P O S I T I O N E D TO D E L I V E R AGA I N ST ST R AT E G I C P L A N Dimerix HQ 425 Smith St, Fitzroy 3065 Victoria, Australia T. 1300 813 321 E. investor@dimerix.com (ASX:DXB) A biopharmaceutical company developing innovative new therapies in areas with unmet medical needs, with a core focus on inflammatory disease treatments such as kidney and respiratory diseases. ESG Statement Dimerix is committed to integrating Environmental, Social and Governance (ESG) considerations across the development cycle of its programs, processes and decision making. The Dimerix commitment to improve its ESG performance demonstrate a strong, well-informed management attitude and a values led culture that is both alert and responsive to the challenges and opportunities of doing business responsibly and sustainably. For personal use only
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Previous experience: • Senior pharmaceutical executive with a demonstrated record of achievement and leadership over more than 30 years within the pharmaceutical and biotechnology industries • Significant accomplishments in capital raising initiatives, pipeline development and licensing ✓ BSc − Chemistry ✓ MBA − Business Previous experience: • Experienced in product development, commercial strategy development & execution • Successfully commercialized pharmaceutical products globally ✓ BSc (Hons) − Pharmacology ✓ PhD − Pharmaceutics ✓ MBA − Business ✓ M.IP.Law − Intellectual Property Law Previous experience: • Extensive biotech drug development & commercial manufacturing experience • Responsible for successful global commercialization programs & NDA registrations ✓ BSc (Hons) − Chemistry ✓ MBA − Business Previous experience: • Experienced executive in pharmaceutical operations • Background in small molecules development and analytical development ✓ BSc (Hons) − Chemistry ✓ PhD – Industrial Chemistry Previous experience: • Experienced technology and governance professional with a focus in operations, risk management, assurance, and AI • Provides advisory services to a family office with multiple Australian biotech investments ✓ BEng (Hons) − Chemical Engineering ✓ BCom − Commerce (Faulding)(1) 1. Acquired by Pfizer in 2015; 2. Acquired by Pfizer in 2009 (2) (1) Dimerix board For personal use only
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Dimerix management Previous experience: • Experienced in product development, commercial strategy development & execution • Successfully commercialised multiple pharmaceutical products ✓ BSc (Hons) − Pharmacology ✓ PhD − Pharmaceutics ✓ MBA − Business ✓ M.IP.Law − Intellectual Property Law (1) 1. Acquired by Pfizer in 2009; 2. Acquired by Pfizer in 2015 Previous experience: • Experienced CFO & Co.Sec • Expertise in Corporate Governance, financial reporting, cash flow management, taxation (including R&D Tax Incentive) & budgeting/forecasting ✓ Bcomm – Commerce ✓ G.Dip. - Financial Planning ✓ M.Acc. – Accounting ✓ GIA(Cert) ✓ Chartered Accountant Previous experience: • 35 years international experience in drug development, commercialization and corporate leadership • Planning, Financing, Pre-clinical, Clinical Development, Regulatory Approval, Product Launch, Pharmacovigilance, and Medical Affairs ✓ B.Pharm (Hons) - Pharmacy ✓ MBBS - Medicine and Surgery Previous experience: • Experienced pharmaceutical executive in project management, clinical development and research translation • BD and strategic alliance leader • Led multidisciplinary R&D&C teams for 13 years ✓ BSc (Hons) – Genetics ✓ PhD – Molecular Immunology ✓ MBA – Business & Leadership Previous experience: • Experienced pharmaceutical executive in Manufacturing (CMC) • Successfully developed and submitted multiple dossiers to FDA, EMA, TGA • Background in project management, technical transfer and product launch ✓ BSc (Hons) – Applied Biology ✓ MBA - Business (2) For personal use only
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Medical Advisory Board Professor of Clinical Trials and Personalized Medicine: University Medical Center Groningen, the Netherlands. He specializes in the research of novel treatment approaches to slow the onset of diabetic cardiovascular and renal disease. Hiddo has been instrumental in interactions between industry, researchers and regulatory agencies in the validation of surrogate endpoints for renal trials. Professor of Medicine & Molecular & Cellular Pharmacology: University of Miami. Chief of the Katz Family Division of Nephrology and Hypertension. She has an extensive history of translational excellence for patients with renal disease and has uncovered novel pathogenetic mechanisms and therapeutic approaches for glomerular disorders. Mayer Professor of Renal Medicine: Department of Cardiovascular Sciences; University of Leicester and Nephrologist. Jonathan is the IgA nephropathy Rare Disease Group lead for the UK National Registry of Rare Kidney Diseases (RaDaR) and a member of the steering committee for the International IgA Nephropathy Network. An attending physician and Director of the Kidney and Blood Pressure Center in the Division of Nephrology at Tufts Medical Center. Lesley’s major research interest is in the estimation and measurement of glomerular filtration rate (GFR) and in defining alternative endpoints for CKD progression trials based on GFR decline and changes in albuminuria. Renal Physician and Head of the Renal Clinical trials at the Royal North Shore hospital, Sydney, Australia. Muh Geot’s main areas of research are in understanding the mechanisms of kidney fibrosis, biomarkers research, and identifying strategies in delaying progressive kidney disease including glomerular diseases. Graduated from Haverford College and the University of Pennsylvania School of Medicine. He has been a practicing pediatric nephrologist for 35 years. Has been the PI of NIDDK and industry sponsored clinical trials in glomerular disease and am a Co-Investigator in the NEPTUNE and CureGN observational cohort studies. Assistant Professor in the Division of Nephrology at the University of Michigan. Interest in observational studies in glomerular disease, including NEPTUNE and CureGN. Lead on PARASOL program to define FSGS endpoints with by applying statistical methods for clinical outcome definition and prediction of kidney disease progression. For personal use only
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Renal disease landscape “A squeaky wheel waiting for grease: 50 years of kidney disease management in the US”1 2018: workshops and regulatory acceptance of surrogate end points in trials of kidney diseases 2 2019 changes in US federal policy and rapid adoption of treatment guidelines have contributed to a sea change in the management of renal disease 3 Historical lack of incentives and public policy have contributed to high costs and poor health outcomes for renal patients1 Public health policy, legislation and product innovation have converged to accelerate change in renal space today “More change in the past 24 months than the past 24 years: The rapid evolution of [kidney disease] management”1 1.Garibaldi A, et al (2021) The Evolution of Kidney Health Management and the Next Frontier; https://www.lek.com/insights/ei/ evolution-kidney-health-management-and-next- frontier; 2. FDA, EMA, National Kidney Foundation Workshop Summary: https://www.kidney.org/news/accelerating -new-clinical-trials-and-treatments-kidney-disease; 3. Thompson, A et al (2019) Change in Estimated GFR and Albuminuria as End Points in Clinical Trials: A Viewpoint From the FDA D OI: 10.1053/j.ajkd.2019.08.007 For personal use only
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Clinical study change: use of surrogate endpoints Pre-2018 2018 2019 2020 2021 "Hard" endpoints for kidney disease (kidney failure) may not be reached for decades1 US FDA, European EMA, and US National Kidney Foundation hold scientific workshop on proteinuria & glomerular filtration rate (GFR) as endpoints for clinical studies in kidney disease2 FDA publish willingness to consider fixed glomerular filtration rate (GFR) and proteinuria decline as surrogate end points for kidney failure in certain conditions3 Publications demonstrate relationship between proteinuria as a continuous variable and kidney survival in FSGS patients4 FDA grants first accelerated approval drug based on proteinuria endpoint in a rare kidney disease, IgA nephropathy5 1.Hartung E, (2015), Pediatric Nephrology volume 31, pages381 –391 DOI: 10.1007/s00467-015-3104-8; 2. FDA, EMA, National Kidney F oundation Workshop Summary: https://www.kidney.org/news/accelerating -new-clinical- trials-and-treatments-kidney-disease; 3. Thompson A et al, (2019) Am J Kidney Dis.; 75(1):4 -5: doi.org/10.1053/j.ajkd.2019.08.007; 4. Troost JP et al, (2020) Am J Kidney Dis.; 77(2):216 -225: doi.org/10.1053/j.ajkd.2020.04.014; 5. FDA Drug Approvals: https://www.fda.gov/drugs/fda-approves-first-drug-decrease-urine-protein-iga-nephropathy-rare-kidney-disease; 6. ASX release 23Dec2021; 5. Predictive Power statistical model, using industry standard as set by the independent renal biostatistician consultant for Dimerix, . Interim Phase 3 analysis data does not guarantee a sta tistically significant outcome at the end of the trial, ASX release 11 March 2024; 2022 Dimerix starts recruiting patients for global Phase 3 study in FSGS patients using approvable surrogate endpoints6 A surrogate endpoint is an intermediate outcome which substitutes the hard endpoint for a disease (e.g. kidney failure), which can take much longer to achieve 2023 2024 FDA led working group, called PARASOL, initiated to assess alternative surrogate endpoints for FSGS Dimerix Phase 3 Interim analysis (n=72 @ 35 weeks) showed DMX-200 performing better than placebo in reducing proteinuria7 For personal use only
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Kidney disease is high interest area for pharma 1. Editorial, Time to sound the alarm about the hidden epidemic of kidney disease, Nature 628, 7-8 (2024) doi: https://doi.org/10.1038/d41586-024-00961-5; 2. The United States Renal Data System (USRDS) Annual Report 2023; (2022 & 2023 estimates based on average growth 2001 -2021) 3. Francis et al. (2024), Nature Rev. Nephrol. https://doi.org/10.1038/s41581-024-00820-6 Prevalence of Kidney Failure, 2001-20232 Year Number of patients Kidney disease is the third-fastest-growing cause of death globally1 • In the US alone, the number of people with kidney failure increased by >200% from 2001 to 20232 • By 2040, it is expected to become the fifth-highest cause of years of life lost1,2 The US government-funded health-care plan (Medicare) spent US$130 billion in 2023 to treat kidney disease patients • the majority being on dialysis1,3 For personal use only
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DMX-200 – working on inflammatory signalling pathway A CCR2 inhibitor working synergistically alongside the current standard of care (AT1R blocker): G protein-coupled receptor (GPCR) 1. ASX release: 09May2022; 2. ASX releases: 14Dec15, 21Nov18, 07Jun21; 3. ASX release and investor presentation 29Jul20 and ASX release 11Mar24 For personal use only
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DMX-200 unique heteromer pharmacology ARB: Irbesartan, * P<0.05 vs sham, # P<0.05 vs un-treated STNx, f P<0.05 vs STNx+Irb. Ayoub MA, et al. (2015) PLoS ONE 10(3): e0119803. 1. FDA written correspondence Macrophage infiltration Proteinuria Retained podocyte numbers Proposed non-clinical safety package suitability for NDA confirmed with FDA1 Proprietary discovery platform (Receptor-HIT) identified: • Formation of AT1R and CCR2 heteromers; • Novel pharmacology (potentiation of signaling) • Dual antagonism required for completed inhibition For personal use only
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DMX-200 Phase 2 effect on inflammatory biomarker1 uMCR = Urinary MCP-1 creatine ratio; PCR = protein creatinine ratio; *placebo adjusted difference 1. ASX presentation 27 October 2020; 2. Liu Y. et al (2024) Role of MCP-1 as an inflammatory biomarker in nephropathy, Front. Immunol., Sec. Inflammation doi.org/10.3389/fimmu.2023.1303076 Average baseline MCP-1 versus average baseline proteinuria MCP-1 levels reduced when on DMX- 200 treatment 0 5 10 15 0.0 0.5 1.0 1.5 Time uMCR normalised uMCR normalised to baseline v time N=7, GeoMean On active On placebo (weeks) -37%* -39%* 50% 0% -50% high MCP-1 correlates to high proteinuria Change in MCP-1 over time on DMX-200 versus placebo • 16 weeks treatment with DMX-200 vs placebo reduced inflammatory biomarker by 39%: ▪ DMX-200 blocks receptor responsible for inflammation ▪ Translates to reduced inflammation and subsequent fibrosis (scarring) in the kidney2 For personal use only
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Intellectual property and exclusivity DMX-200 2032 Method of Use Granted3 any CCR2 inhibitor with any ARB for any kidney disease 2042 Method of Use Global application1 any CCR2 antagonist with any endothelin A receptor for any disease 2042 Formulation Global application1 Any CCR2 antagonist with excipients for use in kidney or respiratory disease Granted patents in key territories including Canada, China, Hong Kong and Japan3 Paediatric exclusivity period 7/10 years Orphan exclusivity2 in many territories 1. If patent applications are granted: PCT/AU2022/050013 and PCT/AU2022/050249; 2. DMX -200 is an NCE: active moiety not approved before which can attract exclusivity periods in various territories; 3. Granted patents US9,314,450; US10,058,555; US10,525,038; CN2012800046165; CA2,821,985; EP12734251.7; HK 4104477.8; IL22741 4; JP2013-547780; SA203/5897; AU2012206945 For personal use only