Cormedix Inc. · NASDAQ:CRMD
Cormedix — Technical Presentation (May 2019)
29 slides from Cormedix's technical presentation, May 10, 2019
Slide 1: LOCK-IT-100 Phase III Study of Neutrolin in Hemodialysis
LOCK-IT-100 A Phase III, Prospective, Multicenter, Double-Blind, Randomized, Active Control Study to Demonstrate the Safety and Effectiveness of Neutrolin® in Preventing Catheter-Related Bloodstream Infections in Subjects Receiving Hemodialysis Therapy as Treatment for End Stage Renal Disease Dr. An
Slide 2: Disclosure Information
Disclosure Information • Dr. Anil Agarwal, Professor Medicine, Ohio State University is a consultant to CorMedix Inc. • Dr. Prabir Roy-Chaudhury, Professor Medicine, University of North Carolina, is a consultant to CorMedix Inc, WL Gore, Medtronic, Bard-BD, Humacyte, Akebia, Vifor-Relypsa, and Bayer
Slide 3: Learning Objectives
Learning Objectives Discuss the results of LOCK-IT-100, a landmark randomized, controlled trial of an investigational catheter lock solution (CLS) containing taurolidine, which demonstrated a statistically significant reduction in catheter-related bloodstream infections (CRBSIs) in patients on hemod
Slide 4: Background
Background • Infections are the 2nd leading cause of death in HD patients • HD patients are at risk for bloodstream and vascular access infections due to immuno-compromised status and frequent vascular access • Although central venous catheters (CVC) comprise only 18.8% of HD vascular accesses they
Slide 5: Neutrolin Catheter Lock Solution in the EU
Neutrolin® Catheter Lock Solution in the EU (1.35% Taurolidine; 3.5% citrate;1000 U/mL Heparin) Approved in EU via CE Mark as Class III Medical Device in multiple indications that require use of a tunneled, cuffed CVC for vascular access to prevent CRBSIs and to maintain catheter patency: • Hemodial
Slide 6: Neutrolin Mechanism of Action
Neutrolin® Mechanism of Action • Taurolidine denatures surface proteins and chemically alters membrane lipids • Taurolidine has broad spectrum antibacterial and antifungal activity and a mechanism of action that does not lend itself to microbial resistance • Antimicrobial resistance has not been ide
Slide 7: Neutrolin CLS: Mode of Administration
Neutrolin® CLS: Mode of Administration • Neutrolin is instilled in the HD arterial and venous lumens following each dialysis session to the fill volume of each lumen • It is aspirated, not flushed, before initiation of the next HD session • There is no intended systemic administration
Slide 8: Taurolidine, Citrate, Heparin (TCH) CLS in HD
Taurolidine, Citrate, Heparin (TCH) CLS in HD Previous Open Clinical Studies in EU Showed Benefit • Reidenberg et al. (2017) showed Neutrolin reduced CRBSIs compared to recent CRBSI rates in HD • Murray et al. (2014) showed TCH reduced staph bacteremia compared to historical heparin controls • Solom
Slide 9: Neutrolin Catheter Lock Solution in the US
Neutrolin®Catheter Lock Solution in the US • Neutrolin is an investigational new drug being developed as a catheter lock solution (CLS) to prevent CRBSI in patients with ESRD receiving HD through a CVC • FDA has awarded Fast Track status and Qualified Infectious Disease Product Designation • The LOC
Slide 10: LOCK-IT-100: Primary Objective
LOCK-IT-100: Primary Objective • To determine the efficacy and safety of Neutrolin as a catheter lock solution compared to heparin (1000 Units/mL) to reduce CRBSI in ESRD subjects • Primary Endpoint: Time to CRBSI • Sample Size: 80% power to determine 55% reduction with two-sided 5% alpha level requ
Slide 11: LOCK-IT-100: Secondary Endpoints
LOCK-IT-100: Secondary Endpoints • Catheter removal for any reason – not needed because of mature AV fistula – due to catheter malfunction • Loss of catheter patency defined as: 1. rt-PA administration or 2. catheter removal due to malfunction
Slide 12: CRBSI Definitions of Signs and Symptoms
LOCK-IT-100: CRBSI Definitions of Signs and Symptoms One or more: 1. Fever at or above 37.8o C; 2. Rigors documented by a medical professional • AND Two or more: 1. Tachycardia >100 bpm; 2. Tachypnea > 24/min; 3. SBP < 90 mm Hg or decrease > 30 mmHg; 4. Obvious change in mental status from documente
Slide 13: CRBSI Definitions of Signs and Symptoms
LOCK-IT-100: CRBSI Definitions of Signs and Symptoms • One positive blood culture (other than for coagulase negative Staphylococcus which requires a confirmatory culture) from: 1. A peripheral venipuncture; or 2. The arterial or venous dialysis port (or the venous or arterial dialysis circuit blood
Slide 14: Definition of Study Completion
LOCK-IT-100: Definition of Study Completion • All assessments through study closure • CRBSI meeting study definition • Catheter removal for any reason • Death • Transfer to a non-study site • Termination of dialysis
Slide 15: Key Inclusion Criteria
LOCK-IT-100: Key Inclusion Criteria • ESRD with HD at least twice-per-week • HD catheter flow at least 250 ml/min • Int. jugular or subclavian site with tip in RA-SVC junction • Life expectancy at least 180 days • CVC use for at least 60 days going forward • Single pool Kt/V > 1.2 over last 30 days
Slide 16: Key Exclusion Criteria
LOCK-IT-100: Key Exclusion Criteria • Antibiotics within last 14 days • Compromised catheter exit site • rt-PA use within previous 30 days with current catheter • Fill volume of catheter lumen unknown • Use of antimicrobial- or heparin-coated catheter • Active or chronic bleeding diathesis in prior
Slide 17: Baseline Demographics (I)
LOCK-IT-100 Baseline Demographics (I) Randomized Population Demographic Neutrolin (403) Heparin (403) % % Mean age (years) (SD) 60.8 (14.22) 60.9 (14.39) <65 years (%) 59.3 58.6 ≥ 65 to < 75 years (%) 24.6 23.6 ≥ 75 years (%) 16.1 17.9 Female (%) 45.7 38.2 White (%) 61.5 65.0 Black or African-Americ
Slide 18: Baseline Demographics (II)
LOCK-IT-100 Baseline Demographics (II) Randomized Population Demographic Neutrolin (403) Heparin (403) % % Other Race (%) 3.4 2.7 Hispanic or Latino Ethnicity (%) 43.9 46.9 Diabetes (%) 69.0 68.7 BMI (mean) kg/m2 29.7 29.2 Months Since 1st Dialysis (SD) 21.2 (37.5) 19.8 (37.0) ≤ 12 Months on Dialysi
Slide 19: Primary Endpoint Analysis
LOCK-IT-100: Primary Endpoint Analysis • The planned maximum number of events for the primary endpoint was 56 CAC-adjudicated CRBSIs • A planned interim analysis was to be conducted on the first 28 cases • At the interim analysis, the unblinded results of the primary endpoint analysis and Serious Ad
Slide 20: Primary Endpoint Interim Analysis at 28 CRBSIs
LOCK-IT-100 Primary Endpoint Interim Analysis at 28 CRBSIs Neutrolin Heparin (N=327) (N=326) No. (CRBSI/1000 CD) 6 (0.136) 22 (0.491) Total Catheter-Days 43,957 44,823 Follow-up Hazard Ratio (95% CI)** 0.28 (0.11, 0.70) p-value* .0034 CD= Catheter-Days * Log-Rank Test ** Cox Proportional Hazards Mod
Slide 21: Primary Endpoint Full Analysis Population at 41 CRBSIs
LOCK-IT-100 Primary Endpoint Full Analysis Population at 41 CRBSIs Neutrolin Heparin (N=397) (N=398) No. (CRBSI/1000 CD) 9(0.133) 32(0.465) Total Catheter Days Follow-up 67,593 68,890 Hazard Ratio (95% CI)** 0.29 (0.14, 0.62) p-value* .0006 CD= Catheter-Days * Log-Rank Test ** Cox Proportional Hazar
Slide 22: Secondary Endpoint: Catheter Removal for Any Reason
LOCK-IT-100 Secondary Endpoint Catheter Removal for Any Reason Full Population Analysis at 41 CRBSIs Neutrolin Heparin (N=397) (N=398) Subjects with CVC Removal (%) 236 (59.4) 225 (56.5) Median Time (days) (95% CI) 197 (171,224) 225 (187,248) Event Rate/1000 CD 3.48 3.23 p-value* 0.416 Cox-Proportio
Slide 23: Secondary Endpoint: Catheter Removal for Positive Reasons
LOCK-IT-100 Secondary Endpoint Catheter Removal for Positive Reasons Full Population Analysis at 41 CRBSIs Post-Hoc Neutrolin Heparin (N=397) (N=398) No Longer Needed for HD 162 131 Improved Renal Function 0 1 Total Removals-Positive Reasons 162 (41) 132 (33) Total Catheter-Days Follow-up 67,780 69,
Slide 24: Secondary Endpoint: Catheter Removal for Negative Reasons
LOCK-IT-100 Secondary Endpoint Catheter Removal for Negative Reasons Full Population Analysis at 41 CRBSIs Post-Hoc Neutrolin Heparin (N=397) (N=398) CRBSI (%) 8 (2.0) 29 (7.3) All Cath. Malfunction-Dysfunction (%) 62 (16) 57 (14) Other (%) 4 (1.0) 7 (1.8) Total 74 (19) 93 (23) Total Catheter-Days F
Slide 25: Secondary Endpoint: Loss of Catheter Patency
LOCK-IT-100 Secondary Endpoint Loss of Catheter Patency Full Population Analysis at 41 CRBSIs Neutrolin (N=397) Heparin (N=398) (%) (%) Loss of Catheter Patency (%) 63 (16) 48 (12) rt-PA for Loss of Patency (%) 46 (12) 33 (8.3) Catheter removal for Loss of 17 (4.3) 15 (3.8) Patency (%) Total Cathete
Slide 26: Safety: Treatment Emergent Serious Adverse Events
LOCK-IT-100 Safety Treatment Emergent Serious Adverse Events Incidence ≥2% in Either Treatment Arm (Safety Population) Deaths & AE Preferred Terms Neutrolin (N=398) Heparin (N=399) % % Deaths 4.5 5.3 Device-related Infection 1.5 2.0 Pneumonia 3.0 5.3 Sepsis 2.3 3.5 Acute Myocardial Infarction 1.3 3.
Slide 27: Primary Outcome: Significant Reduction in CRBSIs
LOCK-IT-100 Primary Outcome Significant Reduction in CRBSIs
Slide 28: Conclusion
Conclusion • LOCK-IT-100, a landmark study, showed that in ESRD subjects with hemodialysis via a central venous catheter, Neutrolin® catheter lock solution significantly reduced catheter-related bloodstream infections, a leading cause of mortality in HD • Compared to heparin, there was no significan
Slide 29: Supplementary Resources
Supplementary Resources • Reidenberg BE, Wanner C, Polsky B, Castanheira M, Shelip A, Stalleicken D, Pfaffle AE. Postmarketing experience with Neutrolin (taurolidine, heparin, calcium citrate) catheter lock solution in hemodialysis patients. Eur J Clin. Microbiol & Infect. Diseases. https://doi.org/