rinvecalinase alfa (DM-199) / DiaMedica - LARVOL DELTA

Integrating Endothelium-Derived Hyperpolarization, Nitric Oxide, and Prostacyclin Pathways: The Multimodal Potential of Human Tissue Kallikrein-1. (PubMed, Vasc Biol) - "Its recombinant form, rinvecalinase alfa (DM199), has demonstrated consistent benefit in early-phase clinical trials, supporting its potential to restore endothelial balance. By reactivating these complementary vasodilatory pathways, DM199 improves microvascular perfusion and endothelial resilience, positioning it as a prototype multimodal therapy for microvascular diseases."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Dementia • Gynecology

Safety and Tolerability of Rinvecalinase Alfa (DM199) for Acute Ischemic Stroke (ReMEDy1). (PubMed, Int J Stroke) - P2 | "Post-hoc analyses in patients not treated with EVT suggested a tendency towards improved excellent global outcomes with rinvecalinase alfa.ConclusionsRinvecalinase alfa appeared to be safe and generally well-tolerated in ischemic stroke patients, with potential efficacy in reducing stroke progression. Further studies are needed to confirm efficacy and long-term benefits in patients without EVT.Registrationshttps://www.clinicaltrials.gov/study/NCT03290560."

Clinical • Journal • Candidiasis • Cardiovascular • Constipation • Gastroenterology • Gastrointestinal Disorder • Ischemic stroke

PE: DM199 for Pregnancy Complications (clinicaltrials.gov) - P=N/A | N=0 | Withdrawn | Sponsor: DiaMedica Therapeutics Inc | N=120 ➔ 0 | Trial completion date: Nov 2026 ➔ May 2025 | Initiation date: Nov 2024 ➔ May 2025 | Recruiting ➔ Withdrawn | Trial primary completion date: Nov 2026 ➔ May 2025

Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Trial withdrawal • Gynecology

ASSESSING SAFETY AND CLINICAL OUTCOMES OF RINVECALINASE ALFA (DM199) IN ACUTE ISCHEMIC STROKE PATIENTS PRE-TREATED WITH INTRAVENOUS THROMBOLYTICS ONLY (ESOC 2025) - "Alteplase-treated patients required NIHSS assessment ≥1-hour post-reperfusion. Rinvecalinase alfa is generally safe and may benefit patients who received IVT and have residual neurologic deficits after IVT. These patients may have unsuccessful recanalization, artery reocclusion, artery-to-artery embolism, or no- reflow phenomenon, and may benefit from rinvecalinase alfa's potential to enhance collateral circulation and salvage penumbra."

Clinical • Clinical data • Cardiovascular • Ischemic stroke

A Phase 1C, Open Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of DM199 Administered Intravenously with a Polyvinyl Chloride Bag in Adult Healthy Subjects and Adults Recently Taking Angiotensin-Converting Enzyme Inhibitors. (PubMed, Clin Pharmacol Drug Dev) - "The study was performed following prior PK analyses revealing that DM199 exposure was greater when administered with polyvinyl chloride infusion materials compared with polyolefin infusion materials. This study supports a revised dosing strategy for DM199 in the ongoing ReMEDy2 trial for AIS and highlights the need for careful consideration of the risk-benefit profile in the clinical context of AIS treatment."

Journal • PK/PD data • Cardiovascular • Ischemic stroke • Pain

PE: DM199 for Pregnancy Complications (clinicaltrials.gov) - P=N/A | N=120 | Recruiting | Sponsor: DiaMedica Therapeutics Inc

New trial • Gynecology

Recombinant Human Tissue Kallikrein-1 for Treating Acute Ischemic Stroke and Preventing Recurrence. (PubMed, Stroke) - "A prior phase II trial demonstrated a favorable impact on clinical outcomes and recurrent strokes, particularly among patients who were not eligible for mechanical thrombectomy. A phase II/III trial has launched in this population, though opportunities for combination revascularization therapies deserve further investigation."

Journal • Review • Cardiovascular • CNS Disorders • Hypotension • Ischemic stroke

DiaMedica Therapeutics Announces Publication of DM199’s Mechanism of Action for the Treatment of Acute Ischemic Stroke (AIS) in the Journal Stroke (Businesswire) - "DiaMedica Therapeutics Inc...today announced the peer-reviewed publication...The article describes the mechanism of action of DM199 (rinvecalinase alfa), a recombinant form of human tissue kallikrein-1, and its scientific rationale in the Company’s ongoing Phase 2/3 trial for acute ischemic stroke (ReMEDy2 Trial)...In animal studies of acute stroke, bradykinin B2 receptor expression on brain endothelial cells in the ischemic region increased 36-fold. In this environment, newly generated bradykinin from DM199 induces potent local vasodilation and improves brain perfusion through three synergistic signaling pathways downstream of the B2 receptor."

Clinical • Preclinical • Ischemic stroke

Treatment of Acute Ischemic Stroke (ReMEDy2 Trial) (clinicaltrials.gov) - P2/3 | N=728 | Recruiting | Sponsor: DiaMedica Therapeutics Inc | Trial completion date: Mar 2026 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

Treatment of Acute Ischemic Stroke (ReMEDy2 Trial) (clinicaltrials.gov) - P2/3 | N=728 | Recruiting | Sponsor: DiaMedica Therapeutics Inc | Active, not recruiting ➔ Recruiting

Enrollment open • Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

Treatment of Acute Ischemic Stroke (ReMEDy2 Trial) (clinicaltrials.gov) - P2/3 | N=728 | Active, not recruiting | Sponsor: DiaMedica Therapeutics Inc | N=339 ➔ 728

Enrollment change • Cardiovascular • Ischemic stroke

Treatment of Acute Ischemic Stroke (ReMEDy2 Trial) (clinicaltrials.gov) - P2/3 | N=339 | Active, not recruiting | Sponsor: DiaMedica Therapeutics Inc | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

Treatment of Acute Ischemic Stroke (ReMEDy2 Trial) (clinicaltrials.gov) - P2/3 | N=364 | Active, not recruiting | Sponsor: DiaMedica Therapeutics Inc | Trial completion date: Sep 2024 ➔ Mar 2025 | Trial primary completion date: Sep 2023 ➔ Mar 2025

Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

Treatment of Acute Ischemic Stroke (ReMEDy2 Trial) (clinicaltrials.gov) - P2/3 | N=364 | Active, not recruiting | Sponsor: DiaMedica Therapeutics Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Ischemic stroke

Multiple Doses of DM199 in Patients With Chronic Kidney Disease (REDUX) (clinicaltrials.gov) - P2 | N=79 | Completed | Sponsor: DiaMedica Therapeutics Inc | Recruiting ➔ Completed | Trial completion date: Dec 2021 ➔ Mar 2022 | Trial primary completion date: Dec 2021 ➔ Mar 2022

Trial completion • Trial completion date • Trial primary completion date • Chronic Kidney Disease • Nephrology • Renal Disease • CRP • CST3 • MMP9 • TNFA • VEGFA

[VIRTUAL] REDUX: A Multicenter, Open-Label Study of DM199 (Recombinant Human Tissue Kallikrein-1) in Patients with Stage 2 or 3 CKD (KIDNEY WEEK 2021) - "Conclusion These data provide clinical validation of the meaningful biologic activity of the recombinant KLK1 (DM199) and support the potential of achieving clinical benefit in patients with CKD. Enrollment is continuing in the AA/CKD and IgAN cohorts."

Clinical • Late-breaking abstract • Chronic Kidney Disease • Diabetic Nephropathy • Fibrosis • Glomerulonephritis • Hypertension • IgA Nephropathy • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Treatment of Acute Ischemic Stroke (ReMEDy II Trial) (clinicaltrials.gov) - P2/3; N=364; Recruiting; Sponsor: DiaMedica Therapeutics Inc; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Cardiovascular • Ischemic stroke • MMP9

Treatment of Acute Ischemic Stroke (ReMEDy II Trial) (clinicaltrials.gov) - P2/3; N=364; Not yet recruiting; Sponsor: DiaMedica Therapeutics Inc

Clinical • New P2/3 trial • Cardiovascular • Ischemic stroke • MMP9

Multiple Doses of DM199 in Patients With Chronic Kidney Disease (clinicaltrials.gov) - P2; N=90; Recruiting; Sponsor: DiaMedica Therapeutics Inc; Trial completion date: Dec 2020 ➔ Dec 2021; Trial primary completion date: Dec 2020 ➔ Dec 2021

Trial completion date • Trial primary completion date • Chronic Kidney Disease • Nephrology • Renal Disease • CRP • CST3 • MMP9 • TNFA • VEGFA

[VIRTUAL] REDUX: A Multicenter, Open-label Study of DM199 (recombinant human tissue kallikrein-1) in Patients with Stage II or III Chronic Kidney Disease (NKF-SCM 2021) - "CONCLUSION Treatments for patients with CKD and IgA nephropathy or type 2 diabetes do not routinely improve kidney function. Results from this Phase 2 study are expected to provide proof-of-concept for the effectiveness, safety, and tolerability of DM199 in specific subgroups of patients with Stage II or III CKD."

Clinical • Chronic Kidney Disease • Diabetic Nephropathy • Fibrosis • Glomerulonephritis • Hypertension • IgA Nephropathy • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

[VIRTUAL] Clinical Significance of Kallikrein Protein (KLK1) Levels Following DM199 in Patients with Diabetes and Chronic Kidney Disease (NKF-SCM 2021) - "CONCLUSION Previous studies in patients with CKD and acute ischemic stroke demonstrated the safety and PK profile of DM199. This analysis provides data to support the rationale for using DM199 to increase KLK1 levels as a treatment in patient populations with CKD."

Clinical • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Fibrosis • Glomerulonephritis • Hypertension • IgA Nephropathy • Immunology • Inflammation • Ischemic stroke • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

[VIRTUAL] Safety and Tolerability of Recombinant Human Tissue Kallikrein (DM199) in Acute Ischemic Stroke - The ReMEDy Randomized Clinical Trial (ISC 2021) - P2 | "DM199 did not significantly increase serious adverse effects versus placebo. The trial was not designed to assess efficacy and further evaluation of DM199 in a larger trial is warranted."

Clinical • Late-breaking abstract • Cardiovascular • Constipation • Gastroenterology • Gastrointestinal Disorder • Ischemic stroke • Pain

DiaMedica Therapeutics Announces Enrollment of Last Patient in Diabetic Kidney Disease Cohort of Phase 2 REDUX CKD Study (Businesswire) - "DiaMedica Therapeutics Inc. (Nasdaq: DMAC) today announced that the last participant has been enrolled and is on treatment in the diabetic kidney disease Cohort of the Company’s Phase 2 REDUX chronic kidney disease (CKD) study. The Company also announced that enrollment has reached 50% in the IgA Nephropathy and African Americans cohorts....We are looking forward to announcing topline results, anticipated in the second quarter of 2021."

Enrollment closed • P2 data • Renal Disease

Co-harboring of mcr-1 and β-lactamase genes in Pseudomonas aeruginosa by high-resolution melting curve analysis (HRMA): Molecular typing of superbug strains in bloodstream infections (BSI). (PubMed, Infect Genet Evol) - "CRPA strains play an essential role in the spread of antibiotic resistance in BSI. Likewise, the HRMA method was sensitive and specific for the detection of superbugs. Moreover, MLST analysis of a diverse collection of P. aeruginosa from blood culture suggests that particular strains or clonal complexes are associated with antibiotic resistance profile."

Journal

Changing the patterns of hospitalized diabetic foot ulcer (DFU) over a 5-year period in a multi-disciplinary setting in Thailand. (PubMed, BMC Endocr Disord) - "The changing trend of DFU provides an excellent outlook into the inadequacies of our current diabetes care systems and global trend of aging population. After considerable successes in reducing major amputations over the past decade, the current analysis revealed a discouraging change in the healing rate of DFU and a stable pattern of major amputation. The prevalence of PAD among Thai patients with DFU increased significantly and affected the results of DFU treatments. Redefined organization of care with multidisciplinary team approach and coordination with referral centers are urgently required to improve outcomes of DFU."

Clinical • Journal • Cardiovascular • Diabetes • Metabolic Disorders • Peripheral Arterial Disease • Reperfusion Injury • Type 2 Diabetes Mellitus