irbesartan/propagermanium (DMX-200) / Dimerix, Amicus, Fuso Pharma, Advanz Pharma - LARVOL DELTA

ACTION3: A Phase 3 Study of DMX-200 for the Treatment of FSGS (KIDNEY WEEK 2025) - P2a, P3 | "Six Independent Data Monitoring Committee reviews have now been completed with DMX-200 (in combination with an ARB) continuing to be well tolerated with no clinically significant safety concerns identified to date. The study is actively recruiting adult patients at 219 sites in 21 countries (Table 1) with sites open to paediatric recruitment in the UK, USA, Mexico and Argentina."

P3 data • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Inflammation • Nephrology • Pediatrics • Renal Disease • CCR2

Late-stage clinical biotech Dimerix has secured orphan drug designation (ODD) in Japan for its lead asset DMX-200 in Focal Segmental Glomerulosclerosis (FSGS)… (The Australian) - "The designation, granted by the Japanese Ministry of Health, Labour and Welfare (MHLW), provides significant commercial advantages, including 10 years of market exclusivity and pricing premiums....DMX-200, a small molecule inhibitor of the chemokine receptor 2 (CCR2), is currently in the pivotal Phase III ACTION3 trial."

Orphan drug • Focal Segmental Glomerulosclerosis

ACTION3: A Study of the Efficacy and Safety of DMX-200 in Patients With FSGS Who Are Receiving an ARB (clinicaltrials.gov) - P3 | N=286 | Recruiting | Sponsor: Dimerix Bioscience Pty Ltd | Trial completion date: Jun 2026 ➔ Dec 2029 | Trial primary completion date: Jun 2024 ➔ Dec 2029

Trial completion date • Trial primary completion date • Focal Segmental Glomerulosclerosis • Glomerulonephritis

DMX-200 does not induce a haemodynamic effect or an acute change in GFR and has a strong cardiovascular safety profile. (ERA 2025) - P2, P2a, P3 | "DMX-200 is a CCR2 pathway inhibitor currently in a Phase 3 pivotal trial (ACTION3, NCT05183646) in adult patients with biopsy-proven FSGS. As anticipated, data from post-hoc analysis of Phase 2 studies indicate that DMX-200 does not induce a haemodynamic effect or acute change in eGFR. Notably, DMX-200 has a strong cardiovascular safety profile."

Clinical • Cardiovascular • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Renal Disease • CCR2

DMX-200 is effective in reducing urine monocyte chemoattractant protein 1 (MCP-1) levels in patients with FSGS without affecting plasma MCP-1 concentration (ERA 2025) - P2a, P3 | "DMX-200 is a CCR2 pathway inhibitor currently in a Phase 3 pivotal trial (ACTION3, NCT05183646) in patients with biopsy-proven FSGS. Data from pre-clinical studies and post-hoc analysis of Phase2 measures suggest DMX-200 can reduce urine MCP-1 levels without increasing plasma MCP-1 (with corresponding reductions in proteinuria). This profile may be beneficial for the treatment effect of DMX-200 and supports its use in patients with FSGS."

Clinical • Chronic Kidney Disease • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Glomerulonephritis • CCL2 • CCR2

A mid-study update on the ACTION3 pivotal Phase 3 trial assessing DMX-200 in patients with focal segmental glomerulosclerosis (FSGS) (ERA 2025) - P2a, P3 | "DMX-200 (repagermanium) has shown encouraging signs of safety and efficacy in combination with an ARB for the treatment of FSGS. The contributing countries and baseline characteristics of the patients enrolled in ACTION3 are similar to those reported in other recent FSGS trials. No clinically significant safety concerns have been observed in patients enrolled to date in the ACTION3 Phase 3 study."

Clinical • P3 data • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Pediatrics • CCR2

Dimerix and Amicus Therapeutics Announce Exclusive License Agreement for DMX-200 in the United States (GlobeNewswire) - "Dimerix Limited...and Amicus Therapeutics...announced that the two companies have entered into an exclusive license agreement for the commercialization of Dimerix’ Phase 3 drug candidate DMX-200 for all indications, including FSGS, in the United States (U.S.). Dimerix retains all rights to commercialize DMX-200 in all territories other than those already exclusively licensed....DMX-200 is a small molecule inhibitor of the chemokine receptor 2 (CCR2) under development in a pivotal Phase 3 study, ACTION3, for the treatment of Focal Segmental Glomerulosclerosis (FSGS) kidney disease....Full enrollment of ACTION3 is expected by year-end 2025....In a March 2025 Type C meeting, Dimerix successfully aligned with the FDA on proteinuria as an appropriate primary endpoint for traditional marketing approval for DMX-200."

Enrollment status • FDA event • Licensing / partnership • Focal Segmental Glomerulosclerosis

DIMERIX RECEIVES INITIAL UPFRONT PAYMENT FROM FUSO (Listcorp) - "Dimerix Limited...announced that it has received the initial payment of ¥300 million (AU$3.2 million) in line with the recently announced license agreement with FUSO Pharmaceutical Industries, Ltd. (FUSO). Under the agreement, FUSO has been granted exclusive rights to commercialise DMX-200 for FSGS in Japan. However Dimerix retains all rights to commercialise DMX-200 in all territories other than those covered by the FUSO, Advanz Pharma and Taiba license agreements....Under the FUSO agreement, Dimerix may become eligible to receive: ¥400 million (~AU$4.1 million) on the first development milestone being achieved (i.e. the first clinical site initiation in Japan) which is still anticipated to occur in Q1 2025; further potential development milestone payments of up to ¥3.4 billion (~AU$30.6 million2); potential sales milestones of up to ¥6.8 billion (~AU$69.4 million2); as well as being eligible to 15-20% royalties on net sales..."

Financing • Respiratory Diseases

ACTION3 Phase 3 Clinical Trial Assessing the Efficacy and Safety of DMX-200 (Repagermanium): Mid-trial Safety Assessment and Pharmacometric Model-Informed Pediatric Dose Selection (KIDNEY WEEK 2024) - "No safety signal that would preclude paediatric dosing was identified. Based on this comprehensive review of safety, PK data and PopPK modelling of predicted exposure, a dose of 120mg BID will be used for adolescents (12-17 years) who are now being recruited into the ACTION3 study."

Clinical • P3 data • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Inflammation • Pediatrics • Renal Disease • CCR2

Combination of the chemokine receptor type 2 (CCR2) antagonist DMX-200 and candesartan for COVID-19: a randomised controlled trial. (PubMed, BMJ Open) - P2 | "Due to recruitment barriers, the study was unable to determine whether DMX-200 improves clinical outcomes in people with COVID-19."

Clinical • Journal • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CCR2

Inhibitory effect of organogermanium compound 3-(trihydroxygermyl)propanoic acid on fructose-induced glycation of amino compounds. (PubMed, Carbohydr Res) - "3-(Trihydroxygermyl)propanoic acid (THGP), a hydrolysate of poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132, also known as repagermanium), can inhibit glycation between glucose/ribose and amino compounds...Both compounds effectively reduced the production of AGEs individually, and the combination of them led to a synergistic suppression. Therefore, through combination with other antiglycation materials, THGP may cooperatively exhibit glycation-inhibitory effects and be able to suppress the AGE production."

Journal

ACTION3 pivotal Phase 3 & open-label extension study assessing DMX-200 in adult & paediatric patients with focal segmental glomerulosclerosis (FSGS). (ERA-EDTA 2024) - P2a, P3 | "DMX-200 (repagermanium) has shown encouraging signs of safety and efficacy in combination with an ARB for the treatment of FSGS. The contributing countries and baseline characteristics of the patients enrolled in ACTION3 are similar to the populations studied in other recent FSGS trials. No clinically significant safety concerns have been observed in patients enrolled to date in the ACTION3 Phase 3 study."

Clinical • P3 data • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Pediatrics • CCR2

Investigation of Strategies to Block Downstream Effectors of AT1R-Mediated Signalling to Prevent Aneurysm Formation in Marfan Syndrome. (PubMed, Int J Mol Sci) - "TRV027, the combination of barbadin with losartan (25 mg/kg/day), and DMX-200 (90 mg/kg/day) with a low dose of losartan (5 mg/kg/day) did not show a significant beneficial effect. Our results confirm that while losartan effectively halts aneurysm formation in Fbn1C1041G/+ MFS mice, neither TRV027 alone nor any of the other compounds combined with lower doses of losartan demonstrate a notable impact on aneurysm advancement. It appears that complete blockade of AT1R function, achieved by administrating a high dosage of losartan, may be necessary for inhibiting aneurysm progression in MFS."

Journal • Cardiovascular • Genetic Disorders • Inflammation • CCL2 • CCR2

ACTION3 – Phase 3 study of DMX-200 for the treatment of focal segmental glomerulosclerosis (FSGS) (ISN-WCN 2024) - P2a, P3 | "DMX-200 (repagermanium) has shown encouraging signs of safety and efficacy in combination with an ARB for the treatment of FSGS. The baseline characteristics of the patients enrolled in ACTION3 are similar to the populations studied in other recent FSGS trials. No clinically significant safety concerns were observed in FSGS patients during 16 weeks of treatment in Phase 2a, or in patients enrolled to date in the ACTION3 Phase 3 study."

P3 data • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • CCR2

REMAP-CAP: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia (clinicaltrials.gov) - P3 | N=20000 | Recruiting | Sponsor: UMC Utrecht | N=10000 ➔ 20000

Enrollment change • Infectious Disease • Influenza • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

ACTION3 Pivotal Phase 3 Clinical Trial and Open-Label Extension Study Assessing the Efficacy and Safety of DMX-200 (Repagermanium) in Adult and Paediatric Patients with FSGS (KIDNEY WEEK 2023) - "Adolescent patients begin recruitment following a scheduled review of adult PK during the first IA.All patients completing the 104-week study period will be offered access to an open-label extension study of DMX-200 for an additional period of up to 2 years. This period begins 4-weeks after completion of the randomised period, and ensures patients have access to treatment during the regulatory submission and review periods."

Clinical • P3 data • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Pediatrics • Renal Disease • CCR2

ACTION3 PHASE 3 STUDY: EVALUATING A NOVEL THERAPEUTIC STRATEGY OF A CCR2 INHIBITOR (DMX-200) WITH ANGIOTENSIN RECEPTOR BLOCKADE IN FSGS (ERA-EDTA 2023) - "ACTION3 is a Phase 3 randomized, placebo-controlled efficacy and safety trial which evaluates the novel approach of combining an investigational CCR2 inhibitor, DMX-200, with angiotensin receptor blockade in patients with FSGS."

P3 data • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Immune Modulation • CCR2

REMAP-CAP: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia (clinicaltrials.gov) - P3 | N=10000 | Recruiting | Sponsor: UMC Utrecht | Trial completion date: Dec 2025 ➔ Feb 2028 | Trial primary completion date: Dec 2023 ➔ Feb 2026

Trial completion date • Trial primary completion date • Infectious Disease • Influenza • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial. (PubMed, JAMA) - P3 | "In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes."

Clinical • Journal • Cardiovascular • Infectious Disease • Novel Coronavirus Disease

CLARITY 2: Controlled Trial of Angiotensin Receptor Blocker (ARB) & Chemokine Receptor Type 2 (CCR2) Antagonist for the Treatment of COVID-19 (clinicaltrials.gov) - P2 | N=49 | Terminated | Sponsor: University of Sydney | N=600 ➔ 49 | Recruiting ➔ Terminated; Withdrawal of funding support from the trial funder.

Enrollment change • Trial termination • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

ACTION3 Pivotal Phase 3 Study Assessing the CCR2 Inhibitor DMX-200 (Repagermanium) in Adult Patients With Focal Segmental Glomerulosclerosis (FSGS) (KIDNEY WEEK 2022) - "The study is conducted in 11 countries at approximately 75 sites and has started enrolment. The study is expected to be completed in 2026."

Clinical • P3 data • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Immune Modulation • Inflammation • CCR2

ACTION3 Pivotal Phase 3 Study Assessing the CCR2 Inhibitor DMX-200 (Repagermanium) in Adult Patients With Focal Segmental Glomerulosclerosis (FSGS) (KIDNEY WEEK 2022) - "The study is conducted in 11 countries at approximately 75 sites and has started enrolment. The study is expected to be completed in 2026."

Clinical • P3 data • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Immune Modulation • Inflammation • CCR2

The ACTION (AT1R and CCR2 Targets for Inflammatory Nephrosis) Program in Focal Segmental Glomerulosclerosis (KIDNEY WEEK 2022) - "Conclusion These encouraging data suggest that DMX-200 may result in clinically meaningful reduction in proteinuria when added to ARB in patients with primary FSGS. This has led to the initiation of an international Phase 2/3 randomised double-blind, placebo-controlled study (ACTION3) to further evaluate the efficacy of DMX-200 in patients with FSGS receiving an ARB."

Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Metabolic Disorders • Nephrology • CCR2

ACTION3 Pivotal Phase 3 Study Assessing the CCR2 Inhibitor DMX-200 (Repagermanium) in Adult Patients With Focal Segmental Glomerulosclerosis (FSGS) (KIDNEY WEEK 2022) - "The study is conducted in 11 countries at approximately 75 sites and has started enrolment. The study is expected to be completed in 2026."

Clinical • P3 data • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Immune Modulation • Inflammation • CCR2

ACTION: Safety and Effectiveness of Propagermanium in Diabetic Kidney Disease Participants Receiving Irbesartan (clinicaltrials.gov) - P2 | N=45 | Completed | Sponsor: Dimerix Bioscience Pty Ltd | Unknown status ➔ Completed

Trial completion • Diabetic Nephropathy • Nephrology • Renal Disease