Dimerix Limited · ASX:DXB
Dimerix — Investor Presentation (February 2018)
32 slides from Dimerix's investor presentation, Feb 5, 2018
Slide 1: DMX-200 for Chronic Kidney Disease
For personal use only Dimerix DMX-200 for Chronic Kidney Disease ASX: DXB 5th and 6th February 2018 1
Slide 2: Disclaimer
Disclaimer For personal use only Some of the information in this presentation may refer to Dimerix Limited (“Dimerix” or the “Company”) based on information available to it as at the date of this presentation. The information in this presentation is provided in summary form and does not contain all
Slide 3: Dimerix has 4 core assets
Dimerix Limited (ASX:DXB) For personal use only Dimerix has 4 core assets 1. DMX-200 for Focal Segmental Glomerulosclerosis (FSGS)* • Planned Phase 2 trial commencing Q1 2018 • Orphan disease with path to pivotal Phase 3 clinical trial 2. DMX-200 for Diabetic Nephropathy (DN)* • Compelling data from
Slide 4: Experienced board and management
Experienced board and management For personal use only Dr James Williams – Chairman Hugh Alsop – Director • Co-founder of Dimerix and iCeutica (acquired • Accomplished and commercially-focused in 2011 and now with 3 FDA drug approvals) pharmaceutical and biotechnology executive • Co-founder and Inve
Slide 5: Corporate overview
Corporate overview For personal use only Corporate snapshot Share price history ASX code: DXB# Share price (02 Feb 18): $0.12 Market cap: $14.1m Cash (31 Dec 2017)$: $4.16m Shares on issue* 117.5m #Consolidation (20:1) completed 31st October 2017 $Includes Shareholder Entitlement Offer of $3.06m rec
Slide 6: Market value of lead clinical programs – DMX-200 for FSGS and DN
Market value of lead clinical programs – DMX-200 for FSGS and DN For personal use only Focal segmental glomerulosclerosis (FSGS) Diabetic nephropathy (DN) • FSGS is a very serious disease and is characterized • Diabetic nephropathy is the single most common cause of by proteinuria, nephrotic syndrom
Slide 7: DMX-200 Intellectual Property – a licencing opportunity
DMX-200 Intellectual Property – a licencing opportunity For personal use only • Dimerix has granted patents in the USA, Australia and Japan covering our lead program DMX-200 (US patent no. 9,314,450); and pending applications in Europe and other major jurisdictions including • The 9,314,450 patent c
Slide 8: Dimerix receptor-HIT platform
Dimerix receptor-HIT platform For personal use only Receptor-HIT • Patented tool that enables understanding of receptor interactions • Particularly suited to G-Protein Coupled Receptors (GPCRs) – most targeted receptor class for drug discovery • Can identify new uses for existing drugs and drive the
Slide 9: Medical advisory board – FSGS
Medical advisory board – FSGS* For personal use only David Packham – Chair David Power • Director of the Melbourne Renal Research Group • Director of Nephrology at Austin Health and Professorial • More than 30-years experience participating in over Associate at the University of Melbourne 40 interna
Slide 10: Dimerix next steps – months
For personal use only Dimerix next steps – 12 months
Slide 11: DMX-200: FSGS study design – phase efficacy
DMX-200: FSGS study design – phase 2 “efficacy” Q1 2018 start FSGS study outline • Patient group: FSGS (n=10+) For personal use only Primary endpoint • 3-month run-in (to ensure stable disease prior to randomisation) Baseline • Patients randomised to 3-month of 0 1 2 3 4 5 6 7 8 9 continuous treatme
Slide 12: DMX-200: Diabetic Nephropathy (DN) – phase 2b efficacy
DMX-200: Diabetic Nephropathy (DN) – phase 2b “efficacy” For personal use only Phase 2a data supports statistical powering for a placebo controlled diabetic nephropathy trial • Diabetic nephropathy patients had a statistically significant mean reduction in ACR of 35.6% (p=0.0063) • Comparator compan
Slide 13: Significant milestones
Significant milestones For personal use only ü Ongoing – Partnering discussions for FSGS and Diabetic Nephropathy DMX-200 for FSGS DMX-200 for Diabetic Nephropathy q CY18Q1 – Commercial manufacturing agreement q CY18Q1 – Engage Diabetic Medical Advisory Board q CY18Q1 – FSGS Phase 2 study Ethics sub
Slide 14: A Phase 2a Trial of DMX-200 in Diabetic Nephropathy
For personal use only A Phase 2a Trial of DMX-200: Synergistic Blockade of AT1R and CCR2 in a Subgroup of Patients with Diabetic Nephropathy. David Packham, Matthew A Roberts, Steven G Holt, James H Williams, Kathy M Harrison, David A Power.
Slide 15: What is DMX-200?
What is DMX-200? For personal use only • Co-administration of 2 drugs to achieve a synergistic effect • Irbesartan – existing standard of care, angiotensin receptor blocker • Propagermanium – CCR2 antagonist with decades of use in Japan for chronic Hepatitis B • Propagermanium successfully formulate
Slide 16: Dimerix has identified distinct synergy between CCR2 and AT1R
Dimerix has identified distinct synergy between between CCR2 and AT1R For personal use only Receptor Heteromer: Macromolecular complex composed of at least two (functional) receptor units with biochemical properties that are demonstrably different from those of its individual components. Ferre et al
Slide 17: Ideal treatment for type diabetic nephropathy
Ideal treatment for type 2 diabetic nephropathy For personal use only • Reduction in hyperfiltration and glomerular hypertension • Angiotensin II type 1 receptor inhibitors (AT1R) • Prevention of interstitial monocyte and macrophage infiltration and fibrosis • Chemokine blockers (CCR2) • Podocyte pr
Slide 18: The consequence of receptor heteromers
The consequence of receptor heteromers For personal use only • AT1R and CCR2 are both expressed on podocytes (in the kidney) • AT1R and CCR2 signal as monomers and hetromers Receptor AT1R Heteromer AT1R + CCR2 CCR2 AngII MCP-1 AngII MCP-1 Ligand Cell membrane Key downstream Hyper filtration, Monocyt
Slide 19: The consequence of receptor heteromers
The consequence of receptor heteromers For personal use only Block with irbesartan Block with propagermanium Block with both Ligand AngII MCP-1 AngII MCP-1 AngII MCP-1 Cell membrane Signalling continues Signalling blocked Signalling continues 19
Slide 20: CCR2 antagonist propagermanium (PPG)
CCR2 antagonist propagermanium (PPG) For personal use only • Propagermanium is a organometallic compound of germanium • Drug substance licensed in Japan under trade name Serocion® for chronic hepatitis B since 1994, with 2,015 patients treated during trials. • DMX-200 is a proprietary extended relea
Slide 21: Simultaneous inhibition of AT1R and CCR2 in 5/6 nephrectomy rat model
Simultaneous inhibition of AT1R and CCR2 in 5/6 nephrectomy rat model For personal use only Reduced proteinuria 5/6 Nephrectomy Model 500 A model of progressive chronic * Proteinuria (mg/24hours) kidney disease: high proteinuria 400 * * 300 Sustained high proteinuria associated with long term renal
Slide 22: Simultaneous inhibition of AT1R and CCR2 in 5/6 nephrectomy rat model
Simultaneous inhibition of AT1R and CCR2 in 5/6 nephrectomy rat model For personal use only Decreased macrophage infiltration Preservation of podocyte numbers 200 Macrophage numbers/area * 150 # * # * * 100 # #∫ 50 Sham Vehicle PPG IRB PPG+ Sham Vehicle PPG IRB PPG+ IRB IRB *, P<0.05 vs sham; #, P<0
Slide 23: Study design Phase 2a
Study design Phase 2a For personal use only Primary Endpoints (“safety”) Secondary Endpoints (“efficacy signals”) • Incidence and severity of Adverse Events • The proportion of responders, defined as those participants • Clinically significant changes in the safety profile of achieving normalization
Slide 24: DMX-200 Phase 2a study summary (N=27)
DMX-200 Phase 2a study summary (N=27) For personal use only Responders 100 • 13/24 patients had a 30% decrease in PCR • 6/24 patients had a 50% decrease in PCR 50 Δ% PCR from baseline 0 Desired outcome reduction in PCR -50 Patient subgroups Diabetic nephropathy IgA nephropathy Other proteinuric dise
Slide 25: DMX-200 Phase 2a study summary: Diabetics (n=10)
DMX-200 Phase 2a study summary: Diabetics (n=10) For personal use only 100 50 Δ% PCR from baseline 0 -50 -100 P5 P8 3 4 0 1 2 4 5 6 P1 P1 P2 P2 P2 P2 P2 P2 Diabetic Nephropathy Patients 25
Slide 26: Diabetic patient demographics (n=10)
Diabetic patient demographics (n=10) For personal use only Age, sex 66 ± 9 years, range 50-79 Sex Male (n=9) female (n=1) Irbesartan dose 75-300 mg/day, n=9 on 300 mg dose Baseline PCR 256 ± 195 mg/mmol, range 70-700 Baseline eGFR 28 ± 13 mL/min/1.73m2, range 17-59 Baseline serum K 4.7 ± 0.4 mmol/L
Slide 27: Diabetic key safety parameters (n=10)
Diabetic key safety parameters (n=10) For personal use only Serum potassium Mean arterial pressure eGFR 30 30 30 20 20 20 10 10 10 Δ% from baseline Δ% from baseline Δ% from baseline 0 0 0 -10 -10 -10 -20 -20 -20 -30 0 4 8 12 16 20 24 28 0 4 8 12 16 20 24 28 0 4 8 12 16 20 24 28 Weeks of treatment We
Slide 28: Diabetic PCR mean reduction 31.9% n=10
Diabetic PCR mean reduction 31.9% n=10 For personal use only Δ% PCR from baseline (SD) 0 * p=0.0014 -50 30 60 90 150 240 240 240 Propagermanium mg mg mg mg mg mg mg dose -100 0 4 8 12 16 20 24 28 Weeks of treatment * Paired, 2-way t-test 28
Slide 29: Diabetic ACR mean reduction 35.6% n=10
Diabetic ACR mean reduction 35.6% n=10 For personal use only Δ% ACR from baseline (SD) 0 * p=0.0019 -50 30 60 90 150 240 240 240 Propagermanium mg mg mg mg mg mg mg dose -100 0 4 8 12 16 20 24 28 Weeks of treatment * Paired, 2-way t-test 29
Slide 30: Diabetic Total protein mean reduction 34.0% n=10
Diabetic Total protein mean reduction 34.0% n=10 For personal use only Δ% Total protein excretion from baseline (SD) 0 * p=0.0015 -50 30 60 90 150 240 240 240 Propagermanium mg mg mg mg mg mg mg dose -100 0 4 8 12 16 20 24 28 Weeks of treatment * Paired, 2-way t-test 30
Slide 31: DMX-200 Phase 2a scientific conclusions
DMX-200 Phase 2a scientific conclusions For personal use only • AT1R and CCR2 form functional heteromers, and simultaneous inhibition is necessary to completely inhibit signalling and therefore achieve an enhanced effect on reducing proteinuria • Combined inhibition of AT1R and CCR2 is safe in patie
Slide 32: Contact
For personal use only Contact Kathy Harrison Chief Executive Officer +61 419 359 149 kathy.harrison@dimerix.com Dimerix Limited ACN 001 285 230 www.dimerix.com