DMX-200 Phase 2a Data Presentation

1 Dimerix DMX-200 Phase 2a Data 3rdNovember 2017 Disclaimer 2 SomeoftheinformationinthispresentationmayrefertoDimerixLimited(“Dimerix”orthe“Company”)basedoninformationavailabletoitasatthedateofthispresentation.Theinformationinthis presentationisprovidedinsummaryformanddoesnotcontainallinformationnecessarytomakeaninvestmentdecisionregardingDimerix. 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Company strategy DimerixLimited (ASX:DXB) 3 1.Using proprietary “Receptor HIT”drug discovery platform to identify multiple development programs 2.Lead program is DMX-200 in Phase 2 human trials for Chronic Kidney Disease (CKD) •Uses compounds that are already known •Orphan Drug in house development path, targeting Focal Segmental Glomerulosclerosis (FSGS) 3.Positive Phase 2a results –diverse group of patients across multiple sub-groups 4.Compelling Diabetic Nephropathy Data –a licensable opportunity 5.DMX-200 Phase 2b study to provide data for 3 CKD sub-group indications, including FSGS as lead orphan indication and out licence, diabetic nephropathy for out licencing, IgA nephropathy as potential follow on orphan indication with out license opportunity. Corporate overview Corporate Snapshot Major Shareholders (%) 4 ASX Code DXB# Share Price (25 Oct 17) $0.185 Market cap $17m Cash (30 Sep 2017) $1.6m (R&D tax incentive, $545,771 received 17thOctober 2017) Shares on issue* 91.9m Mr Peter Meurs 17.33 Yodambao Pty Ltd 5.11 Mrs Wishney Sritharan Krishnarajah 2.47 White Family 2.21 SRV Custodians Pty Ltd 2.07 Pfleger Family 1.70 Jampaso Pty Ltd (Williams Family) 1.51 *Unlisted Performance Shares: 3.75.m; Options (expire 31 Dec 2017): 0.895m; Options (ESOP): 3.38m Share price history #Consolidation completed 31stOctober 2017 Hugh Alsop –Director •Accomplished and commercially-focused pharmaceutical and biotechnology executive •Responsible for successful global commercialisation programs and NDA registrations David Franklyn –Director •Experienced Director of ASX-listed companies in a variety of sectors •Extensive experience in financial analysis, corporate advice, business management and IR Dr Sonia Poli–Director •Former Senior Management at Hoffman la Roche and Executive at Addex Therapeutics •20 years international experience in small molecule drug development Experienced board and management 5 Dr James Williams –Chairman •Co-founder of Dimerixand iCeutica(acquired in 2011 and now with 3FDA drug approvals) •Co-founder and Investment Director of Yuuwa Capital ($40M venture fund) Kathy Harrison –Chief Executive Officer •20 years operational and strategic experience in drug development including at AMRAD, CytopiaResearch Pty Ltd, PhosphagenicsLtd •Registered Patent Attorney Dr Robert Shepherd –Head of Drug Development •Drug developer with experience in a wide range of projects / therapeutic areas •PhD in biomedical research, and background in finance and project management David Power •Director of Nephrology at Austin Health and Professorial Associate at the University of Melbourne. •Recipient of multiple competitive research grants from the MRC (UK) and the NH&MRC (Australia) and author of over 150 peer-reviewed scientific publications AlessiaFornoni •Chief of Nephrology and Hypertension at the University of Miami Miller School of Medicine and Chair of the Peggy and Harold Katz Drug Discovery Centre. •Vice President & Chief Scientific Officer of L&F Health LLC, a small start-up company focused on finding a cure for patients with kidney disease. Medical advisory board 6 David Packham –Chair •Director of the Melbourne Renal Research Group. •More than 30-years experience participating in over 40 international clinical trials in a variety of chronic kidney conditions,and serves on advisory boards for Astra Zeneca, Otsuka and Vifor. Daniel Cattran •Professor of Medicine at the University of T oronto and Senior Scientist at the T oronto General Research Institute. •Chair of the T oronto Glomerulonephritis Registry, which currently includes over 12,000 cases of biopsy proven GN. Jonathan Hogan •Assistant Professor of Medicine and Clinical Director of the Glomerular Disease Centre at the University of Pennsylvania. •Dr Hogan is a nationally-recognized expert in glomerular diseases and onconephrology, and has published more than 25 papers in peer reviewed medical journals 7 Sources: U.S.Renal Data System,USRDS2013 Annual Data Report: Atlas of End-Stage Renal Disease in the United States,NIH, NIDDK: National Kidney Foundation website www.kidney.orgaccessed 27 October 2017 Chronic kidney disease (CKD) -market opportunity Source: Global Burden of Disease Study 2013 •CKD is a global health problem affecting over 10% of the population with 26 million patients in the US alone •CKD can be cause by a number of different types of disease, or be of unknown cause •CKD gets progressively worse, with patients whose kidneys fail requiring dialysis or kidney transplant •Hemodialysis treatment costs an average of US$89,000 per patient annually in the United States, and caring for people with end stage renal disease costs the US healthcare system US$33billion per annum Important sub-group indications of CKD –FSGS and Diabetic Nephropathy •FSGS is characterized by proteinuria, nephrotic syndrome and rapid progression to end-stage renal disease •DMX-200 has US Orphan Designation for FSGS •A number of studies have found that FSGS patients with reductions in proteinuria have improved kidney survival. 8 Source: Diabetes 2025 –U.S., state and metropolitan trends, Institute for Alternative Futures; Boyle et al. Projection of the year 2050 burden of diabetes in the U.S. adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence, Population Health Metrics, 2010, 8:29; Boer et al. Temporal trends in the prevalence of diabetic kidney disease in the U.S, JAMA. 2011; 305 (24): 2532-2539; www.cdc.gov/diabetes/statistics/prev/national/figpersons.htm Independent analysts estimate Focal Segmental Glomerulosclerosis (FSGS) sub- group drug sales to be worth USD $1 billion per annum in the US alone Source: Persistence Market Research, Diabetic Nephropathy Market Report, 2015 Diabetic nephropathy (DN) •Diabetic nephropathy is the single most common cause of CKD worldwide and is associated with significant increase in cardiovascular morbidity and mortality •US prevalence is estimated as 3% of the population (9 million patients) The North American and global markets are estimated at USD 931m and USD 2,093m in 2014 and are expected to reach USD 1,302.0m USD 2,929min 2020 (respectively Focal segmental glomerulosclerosis (FSGS) Current treatments for CKD •Damaged kidneys “leak”proteins into the urine. This is called proteinuria and is the most common symptom of kidney disease –relevant measure of treatment efficacy (a prognostic indicator of future kidney damage). •First line therapy is reducing blood pressure using angiotensin receptor blockers (such as irbesartan) or ACE inhibitors. •In some types of kidney disease, including the FSGS sub-group, patients are given a cocktail of drugs including immunosuppressantsand steroids such as Prednisone, which have serious and unpleasant side effects •There is a huge unmet medical need for a safe treatment of CKD across the sub-group indications which can significantly reduce proteinuria and prolong the life of the kidney 9 Will in remission Relapse from nephrotic syndrome Comparator Programs 10 •NASDAQ: CCXI •Market Cap: ~US$329 million •Completed Phase 2 for CCX140 in diabetic nephropathy(a CKD sub-group indication)– a CCR2 antagonist •Measured urine albumin creatinine ratio (ACR) change from baseline by 16% over placebo (-2% for placebo and -18% for CCX-140 at best dose) (geometric mean reduction at 12 weeks of 24%) •Viforlicensed CCX-140 from Chemocentryx with Phase 2 data for use outside the US for $50m upfront, undisclosed milestone payment and double digit royalties •NASDAQ: RTRX •Market cap : ~US$ 917 million •Phase 2 asset, sparsentan, for treating FSGS (a CKD sub-group indication)–a dual angiotensin endothelin receptor blocker •Patients removed from Standard of Care treatment 2 weeks prior to dosing •T op line positive data showing improved proteinuria compared with standard of care (irbesartan) at 8 weeks •Standard of Care (Irbesartan) reduced total protein urine excretion per day by 19% and sparsentanby 47.4% (net 28.4%) 11 •DMX-200 is a tablet which is taken in conjunction with existing medications. •Patients continue taking their standard of care medication (irbesartan) and add a second drug to this (propagermanium), a CCR2 antagonist. •This has been confirmed by the US FDA as being an adjunct (not combination) therapy •Both drugs have been in use for many years, and their safety profile is well understood. •Patients on the completed Phase 2a Study had the diagnosis across a number of key sub-groups diabetic nephropathy (10), IgA nephropathy (6), other proteinuricdiseases (11) Trial design •27 patients in open label dose escalation study across 4 sites in Australia •Patients were on stable irbesartan prior to and throughout the study. •Patients additionally received an oral dose of propagermanium •Propagermanium dose escalated at four week intervals, unless proteinuria was within normal limits. DMX-200 –Dimerix lead program for CKD Study Summary 12 The graph shows individual patient PCR** values as % change from baseline value during treatment ranked by PCR reduction level. ** Protein Creatinine Ratio (PCR), a measure of levels of proteinuria and indicator of CKD. An alternate measure is the Albumin Creatinine Ratio (ACR). ** Positive PCR movements highlight possible disease progression during the study •6/24 patients had a 50% decrease in PCR •13/24 patients had a 30% decrease in PCR Responder movements P1P2P3P4*P5P6P7P8P9*P10P11P12P13P14P15P16P17P18P19P20P21P22P23P24P25P26 -100 -50 0 50 100 Δ% PCR from baseline * Patients withdrawn from study before completion Patient subgroups Diabetic nephropathy IgA nephropathy Other proteinuric disease Primary and Secondary end points 13 Primary Endpoint Met: DMX-200 was safe and well tolerated •Adverse events consistent with underlying patient population •No changes in the rate or severity of adverse events with propagermanium. •No clinically significant trends in safety signals from baseline; including blood pressure, eGFR, and serum potassium. Secondary Endpoints: Efficacy demonstrated with particular effect in some patients •25% (6/24) patients achieved were responders: “participants achieving normalization of proteinuria or a 50% reduction in proteinuria”, and is additional to any effect of irbesartan (standard of care) (a 50% reduction is a high criteria level) •Responders at the sub-group level: •83% (5/6) had a primary diagnosis of diabetic nephropathy, and •17% (1/6) had a primary diagnosis of IgA nephropathy •54% (13/24) achieved at least a 30% reduction in PCR at any dose level of propagermanium. Post hoc analysis –averageProtein Creatinine Ratio (PCR) and Albumin Creatinine Ratio (ACR) in Diabetic Nephropathy Group 14 •50% (5/10) of diabetic nephropathy patients showed a greater than 50% reduction from baseline in PCR during treatment. •These compelling data justified additional analysis, based on average responses across the diabetic nephropathy group using both (PCR) as well as the measure used by some competitors (ACR) 0 4 8 12 16 20 24 28 -100 -50 0 50 Δ% PCR from baseline (SD) Weeks of treatment Reduction in PCR (24-hr) of diabetic nephropathy patient cohort (n=10) during combined treatment with irbesartan and propagermanium. p=0.0088 Two-tailed, paired t-test 0 4 8 12 16 20 24 28 -100 -50 0 50 Δ% ACR from baseline (SD) Weeks of treatment Reduction in ACR (24-hr) of diabetic nephropathy patient cohort (n=10) during combined treatment with irbesartan and propagermanium. Two-tailed, paired t-test p=0.0063 15 Post hoc analysis –averageProtein Creatinine Ratio (PCR) and Albumin Creatinine Ratio (ACR) in Diabetic Nephropathy Group •Diabetic nephropathy patients had a statistically significant mean reduction in PCR of 31.9%between baseline and the last two periods of treatment (p=0.0088) •Diabetic nephropathy patients had a statistically significant mean reduction in ACR of 35.6%between baseline and the last two periods of treatment (p=0.0063) DMX-200 –a pipeline in a program 16 Development Path by CKD sub- group (indications) Pre clinical Observational Phase 1 Phase 2a Phase 2b Phase 3 Orphan path/ out license Out license Orphan path/ out license Out License FSGS Diabetic Nephropathy IgANephropathy DiabeticRetinopathy Confidential 17 •Glomerular diseases with an inflammatory component •FSGS an Orphan indication, faster path to market and compelling license opportunity •Diabetic Nephropathyan enormous market potential and compelling data from Phase 2a (greatly exceeded expectations) •Phase 2a data supports statistical powering for the diabetic nephropathy group •IgA nephropathy is one of the most aggressive types of chronic kidney diseases with limited treatment options •1/6 of the patients in our study was a 50% responder –this is unheard of in this condition •Limited treatment options, the most common off-label treatment of this disease recently had a trial terminated due to safety concerns (Jichenget al. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy The TESTING Randomized Clinical Trial, JAMA.2017;318(5):432-442. doi:10.1001/jama.2017.9362) Trial design and Choice of FSGS, DN and IgA On-treatmentScreening Follow-upRun-in Placebo Low dose High dose R 0 3 6 9 1281 2 4 5 7 Baseline Treatment DMX-200 Phase 2b Study Design 18 •Double blind, placebo controlled •Three patient groups: DN(n=60), FSGS plus IgAN(n=30), for total N=90 •3-month run-in to ensure stable disease prior to randomisation •Patients randomisedto 6-month of continuous treatment with low dose of propagermanium, high dose of propagermanium, or placebo. •All patients followed-up for 3-months to determine rebound following treatment •Optional protocols for diabetic retinopathy screening, and collection of patient data during an optional special access program Indicative cohort schedule DMX-200 Phase 2b Study Endpoints 19 Primary Endpoint Secondary Endpoints Exploratory Endpoints •Change in 24-hour ACR from baseline (mean of run-in) to the end of treatment (month 5 & 6)for DN cohort •Incidence and severity of AEs throughout study •Clinically significant changes in the safety profile of participants •Change in 24-hour ACR from baseline (mean of run-in) to the end of treatment (month 5 & 6)for FSGS and IgANcohort •Steady-state plasma PK •Change in PCR,eGFR and total protein excretion •Effect of removing propagermanium on ACR, eGFR, PCR, total protein excretion •Effects on plasma and urine biomarkers of inflammation. •Effect on biomarkers of kidney disease progression. •* Evaluation of safety, tolerability and efficacy in patients that continue to receive propagermanium under compassionate access. •*Change in retinopathy of diabetic patients. * Evaluated under optional protocolsNB: These are subject to final amendmentsin conjunction with MAB and investigators DMX-200 Intellectual Property 20 •Dimerixhas granted patents in the USA, Australia and Japan covering the lead program DMX-200 (US patent no 9,314,450); and pending applications in Europe and other major jurisdictions including •The ‘450 patent covers the use of CCR2 antagonists in conjunction with, or sequential to, administration of angiotensin receptor blockers (ARBs), inclusive of treatment of CKD •Additional applications have been filed for the extended release formulation and dosage regimes •The therapy patent expires in 2032 Significant next steps 21 üHuman pharmacokinetics (PK) study to optimise dose of DMX-200 for extended release formulation on track to complete 2H CY2017 (3 tablets daily reduced down to 2 tablets daily) üPresentation of Phase 2a data by CEO Kathy Harrison at BioEuropeon 7thNovember 2017, a major industry partnering and investment forum üCommencement of Phase 2b trial (recruiting Q1 calendar 2018) üPhase 2a data analysis and Phase 2b study design discussions with big pharma and medical advisory board (ongoing) üFiling Orphan Drug designation in Europe, 2018(US already attained) üMeetings with European Regulatory Advisors (2018). Contact Kathy Harrison Chief Executive Officer +61 419 359 149 [email protected] DimerixLimited ACN 001 285 230 www.dimerix.com Additional Details FSGS: An orphan disease with limited treatment options 24 • Focal segmental glomerulosclerosis (FSGS) is a group of clinical-pathological syndromes sharing a common glomerular scarring lesion and characterized by proteinuria, nephrotic syndrome and rapid progression to end-stage renal disease • The disease is manifested by marked proteinuria (2-10g/day), dyslipidemia, hypoalbuminemia and severe edema • A number of studies have found that FSGS patients with reductions in proteinuria have improved kidney survival. • Troyanovet.al. (2005) found a strong association between reduction of proteinuria (either complete or partial response) and the survival from renal failure in a study of 281 FSGS patients in Canada.* • Limited treatment options: RAS inhibitors => Steroids => Transplant (30-40% recurrence) TroyanovS, Wall CA, Miller JA, ScholeyJW, CattranDC; “Focal and segmental glomerulosclerosis: definition and relevance of a partial remission,” J Am SocNephrol. 2005 Apr;16(4):1061-8. Diabetic Nephropathy 25 • Diabetic nephropathy is the single most common cause of chronic kidney disease worldwide and is associated with significant increase in cardiovascular morbidity and mortality • US prevalence is estimated as 3.0% (9M patients) • The disease is a microvascular complication of longstanding type 1 and type 2 diabetes characterized by albuminuria (abnormal excretion of albumin in the urine), overt nephropathy (proteinuria > .5g/24h and decline in glomerular filtration rate) and hypertension • Diabetic nephropathy may result in end-stage renal disease (ESRD), requiring dialysis or kidney transplantation • The goal of treatment is to prevent the progression from microalbuminuria to overt nephropathy, reduce the rate of renal function decline and occurrence of cardiovascular events • Current treatment: RAS inhibitors; Diuretics Treatment and Referral Algorithm Pre-Diabetic Nephropathy Introduce ACEI or ARB Microalbuminuriaand Hypertension Increase ACEI or ARB Dose End-Stage renal disease Optimize blood pressure control with ARB or ACEI, initiate kidney dialysis or transplant Persistent Microalbuminuria Increase ACEI or ARB dose and refer to nephrologist Overt Nephropathy Increase ACEI or ARB dose and refer to nephrologist, add diuretic as required Type 1 Diabetes Type 2 Diabetes Source: Medscape accessed December 2013; Treatment of diabetic nephropathy, UpToDateaccessed December 2013; Fried et al. Combined angiotensin Inhibition for the treatment of diabetic nephropathy, The New England Journal of Medicine, 2013; Cooper Mark, Pathogenesis prevention and treatment of diabetic nephropathy, The Lancet 352:9123 213-219, 1998 Study Design Phase 2a 26 Screen Baseline Treatment Period Follow Up 30 mg Total N= 27 Total n = 24 60 mg 150 mg 90 mg 240 mg 240 mg 240 mg Total n = 37 4 weeks at each dose level Primary Objectives Secondary Objectives • To determine the safety and tolerability of propagermanium when added to standard irbesartan treatment in participants with proteinuria • To evaluate the effects of propagermanium on various biomarkers when added to standard irbesartan in participants with proteinuria Primary Endpoints Secondary Endpoints • Incidence and severity of AEs • Clinically significant changes in the safety profile of participants (biochemistry, hematology, urinalysis, physical examinations) • The proportion of responders, defined as those participants achieving normalization of proteinuria or a 50% reduction in proteinuria Key InclusionCriteria Key Exclusion Criteria • Adults > 18 years • PCR ≥ 50 mg/mmol (442mg/g)over 24-hours • eGFR 20-60 ml/min/1.73m2 • Serum creatinine men: 115-291 mmol/L (1300-3291 mg/dL), women: 132-309 mmol/L (1492-3494 mg/dL) • Stable irbesartan for 3-months • Rapidly progressing proteinuria • ACE, NSAID or spironolactone • Uncontrolled blood pressure Phase 2a Primary end point -safety 27 • Combined therapy with propagermanium and irbesartan was well tolerated. • Adverse events were consistent with underlying patient and population co-morbidities. • There was no change in the rate of AEs or severity of AEs with dose of propagermanium. • There were no clinically significant trends in biochemistry, hematology, urinalysis hematology or vital signs from baseline during treatment including blood pressure, eGFR, and serum potassium. Overall PPGdose 30mg 60mg 90mg 150mg 240mg All AEs 119 (8.5) 20 (8.8) 16 (7.2) 16 (7.5) 18 (8.1) 49 (9.6) Mild AEs 60 (4.3) 10 (4.4) 12 (5.4) 9 (4.2) 10 (4.5) 19(3.7) Moderate AEs 52 (3.7) 8 (3.5) 4 (1.8) 6 (2.8) 5 (2.2) 29 (5.7) Severe AEs 7(0.5) 2 (0.9) None 1 (0.5) 3 (1.3) 1 (0.2) IP-related AEs* 22 (1.6) 7 (3.1) 3 (1.4) 6(2.8) 1(0.4) 5 (1.0) Serious AEs (SAE)** 9 (0.6) 3 (1.3) None None 2 (0.9) 4 (0.8) Table: T otal number and (annualized rate) of AEs by dose of propagermanium, N=27. * Events assessed by the investigator to be possibly, probably or definitely related to IP ** n=5 patients had an SAE/s during study consistent with their co-morbidities: low hemoglobin (not related to IP), stroke (remotely related to IP), melena/anemia (not related to IP), cholecystitis/pancreatitis (not related to IP), NSTEMI (remotely related to IP), fluid overload (not related to IP), ESRF (not related to IP), and intermittent depression/suicidal ideation (possibly related to IP). Phase 2a Secondary Pre Specified Endpoint -Proteinuria 28 • 24patientscompleteddosingandwereassessedforefficacy. • 6patientsachievedthepre-specifiedcriteriaofresponders:“participantsachievingnormalizationofproteinuriaora 50%reductioninproteinuria”. • Responders appeared to be concentrated among those with a primary diagnosis of diabetic nephropathy, 83% (5/6) of responders had a primary diagnosis of diabetic nephropathy, and 17% of responders (1/6) had a primary diagnosis of IgA nephropathy • Proteinuriaresponseswereallachievedinpatientsreceivingirbesartanforaminimumof3monthspriortoreceiving IP ,andareconsideredadditionaltoanyeffectofirbesartanonproteinuria. • Ofthepatientsthatcompleteddosing,54%(n=13)achievedatleasta30%reductioninPCRatanydoselevelof propagermanium. Figure:PeakreductioninPCR(24-hr)frombaselineforresponders Phase 2a Post hoc analysis 29 • 50% (5/10) of diabetic nephropathy patients showed a greater than 50% reduction from baseline in PCR (24-hr) during treatment. • This compelling data in the diabetic nephropathy group justified additional statistical analysis for that group, based on average responses across the entire group • Diabetic nephropathy patients had a statistically significant mean reduction in PCR (24hr) of 31.9%between baseline and the last two periods of treatment (p=0.0088) • An alternate measure of proteinuria used by some competitors is the albumin creatinine ratio (ACR) • Diabetic nephropathy patients had a statistically significant mean reduction in ACR (24hr) of 35.6%between baseline and the last two periods of treatment (p=0.0063) • T o confirm this finding across all time points, a repeat measures mixed model (linear regression) was used to integrate all PCR (24- hr) measurements across the treatment period. A significant decrease in PCR (24-hr) during treatment was shown (p=0.0159). 0 4 8 12 16 20 24 28 -100 -50 0 50 Δ% PCR from baseline (SD) Weeks of treatment Reduction in PCR (24-hr) of diabetic nephropathy patient cohort (n=10) during combined treatment with irbesartan and propagermanium. p=0.0088 Two-tailed, paired t-test 0 4 8 12 16 20 24 28 -100 -50 0 50 Δ% ACR from baseline (SD) Weeks of treatment Reduction in ACR (24-hr) of diabetic nephropathy patient cohort (n=10) during combined treatment with irbesartan and propagermanium. Two-tailed, paired t-test p=0.0063 DMX-200 Phase 2b Key Inclusion Exclusion Criteria 30 General Inclusion •Adults > 18 to 75 years •BMI 20-40 kg/m2 •Proteinuric disease > 6 months duration •eGFR 40-90 ml/min/1.73m2 •T aking stable (> 3-month) 300 mg irbesartan FSGS cohort •Biopsy-proven primary FSGS or documented genetic mutation •Protein excretion >1 g/day •< 50% fibrosis on most recent biopsy •If using immunosuppressant, stable dosing > 3 months General Exclusion •Use of an ACE or symptomatic use of immunomodulatory agents including steroids •Previous renal transplant or known non-diabetic renal disease, except related to hypertension •BP > 140/90 mmHg or uncontrolled BP •Significant medical conditions related to cardiac, hepatic, or immune function Diabetic nephropathy cohort •Primary renal diagnosis of diabetic nephropathy •Haemoglobin A1c (HbA1c) 6.0- 10.0% •Protein excretion 1-3 g/day •Not using immunosuppressants IgA nephropathy cohort •Biopsy-proven primary IgA nephropathy diagnosis •Protein excretion 1-3 g/day •If using immunosuppressant, stable dosing > 3 months NB: These are subject to final amendments in conjunction with MAB and investigators DMX-200 US IP and data exclusivity strategy for FSGS 31 2017 2018 2019 2020 2021 2022 * 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037 2038 2039 Combination Therapy Patent Dose Patent application NCE Exclusivity US Orphan Drug Exclusivity 30 month stay Patent extension to a maximum of 14 years post approval patent life – measured from the effective date of the IND to the date of filing the NDA Pediatric exclusivity Possible max 4 year patent extension *assumed DMX-200 registration for FSGS Dosage Form (composition)

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