PF-06730512 / Pfizer - LARVOL DELTA

PODO: A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS) (clinicaltrials.gov) - P2 | N=47 | Terminated | Sponsor: Pfizer | N=35 ➔ 47 | Active, not recruiting ➔ Terminated; The study was terminated due to lack of efficacy at both tested doses on 5th December 2022. The decision to terminate the study is not related to a safety concern.

Enrollment change • Trial termination • Focal Segmental Glomerulosclerosis • Glomerulonephritis

PODO: A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS) (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Aug 2025 ➔ Feb 2023 | Trial primary completion date: Aug 2025 ➔ Feb 2023

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

Therapeutic Blockade of the SLIT/ROBO Signaling Pathway Alleviates Podocytopathy Defects in Integrin-Linked Kinase Podocyte-Specific Knockout Mice (KIDNEY WEEK 2022) - P2 | "Our studies provide additional confidence in rationale for blocking the ROBO/SLIT signaling pathway for treating podocytopathies and proteinuric kidney diseases. A phase 2 (NCT03448692) clinical trial testing the efficacy of a ROBO2-Fc fusion protein (PF-06730512) in FSGS patients is ongoing."

Preclinical • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Renal Disease • ROBO2

PODO: A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS) (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=44 ➔ 30

Enrollment change • Enrollment closed • Focal Segmental Glomerulosclerosis • Glomerulonephritis

PODO: A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS) (clinicaltrials.gov) - P2 | N=44 | Recruiting | Sponsor: Pfizer | N=66 ➔ 44

Enrollment change • Focal Segmental Glomerulosclerosis • Glomerulonephritis

PODO: A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS) (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: Pfizer | N=44 ➔ 66 | Trial completion date: Feb 2024 ➔ Aug 2025 | Trial primary completion date: Feb 2024 ➔ Aug 2025

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

[VIRTUAL] PODO: Phase 2 Study of PF-06730512 in Focal Segmental Glomerulosclerosis (FSGS) - Results from First Interim Analysis (KIDNEY WEEK 2021) - P2 | "Conclusion In this interim analysis (n=9), a significant mean reduction in UPCR was observed in FSGS subjects after 12 weeks of treatment with PF-06730512. PF-06730512 thus far is safe and well-tolerated."

Late-breaking abstract • P2 data • Fibrosis • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Immunology • Transplantation • SLIT2

[VIRTUAL] PODO: A Phase 2 Multicenter, Open-Label, Adaptive, Sequential Cohort Trial of PF-06730512 in Adult Subjects With Focal Segmental Glomerulosclerosis (FSGS) (KIDNEY WEEK 2021) - P2 | "ROBO2/SLIT2 signaling negatively regulates nephrin-induced actin polymerization and destabilizes podocyte focal adhesions and attachment to the GBM by inhibiting non-muscle myosin IIA. Secondary endpoints include safety and changes in eGFR. The PODO trial will provide information about the efficacy and safety of PF-06730512 inhibition of the ROBO2 pathway and its impact on podocyte injury in FSGS."

Clinical • P2 data • Fibrosis • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Immunology • Infectious Disease • Transplantation • SLIT2

[VIRTUAL] PODO: A Phase 2 Multicenter, Open-Label, Adaptive, Sequential Cohort Trial of PF-06730512 in Adult Subjects with Focal Segmental Glomerulosclerosis (FSGS) (KIDNEY WEEK 2020) - P2 | "The PODO trial will provide information about the efficacy and safety of PF-06730512 inhibition of the ROBO2 pathway and its impact on podocyte injury in FSGS. Funding: Pfizer Inc"

Clinical • P2 data • Fibrosis • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Immunology • Renal Disease • Transplantation • SLIT2

A Phase 1 first-in-human study of the safety, tolerability, and pharmacokinetics of the ROBO2 fusion protein PF-06730512 in healthy participants. (PubMed, Pharmacol Res Perspect) - P1 | "Further trials in patients with FSGS are warranted. Clinical trial registration: Clinicaltrials.gov: NCT03146065."

Clinical • Journal • P1 data • PK/PD data • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Renal Disease • SLIT2

PODO: Trial Design: Phase 2 Study of PF-06730512 in Focal Segmental Glomerulosclerosis. (PubMed, Kidney Int Rep) - P2 | "This ongoing trial will report the efficacy, safety, pharmacokinetics, and biomarker results of PF-06730512 for patients with FSGS. Findings from this proof-of-concept study may support further development and evaluation of PF-06730512 to treat FSGS and warrant assessment in phase 3 clinical trials."

Journal • P2 data • Chronic Kidney Disease • Fibrosis • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Immunology • Infectious Disease • Nephrology • Renal Disease • Solid Organ Transplantation • Transplantation • SLIT2

PODO: A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS) (clinicaltrials.gov) - P2; N=44; Recruiting; Sponsor: Pfizer; Trial completion date: May 2023 ➔ Feb 2024; Trial primary completion date: May 2023 ➔ Feb 2024

Clinical • Trial completion date • Trial primary completion date • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Renal Disease

[VIRTUAL] A ROBO2 Fusion Protein (PF-06730512) Traps SLIT Ligands and Therapeutically Ameliorates Podocyte Injury (KIDNEY WEEK 2020) - P2 | "We have generated a novel therapeutic ROBO2 fusion protein that functions as a SLIT ligand trap to treat podocyte injury in a pre-clinical animal model. Inhibiting the ROBO2/SLIT2 pathway therapeutically reduces proteinuria and improves podocyte ultrastructure. A phase 2 clinical trial to evaluate the safety and efficacy of ROBO2-Fc (PF-06730512) in patients with FSGS is currently ongoing (NCT03448692)."

Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Renal Disease • Collagen Type IV • SLIT2

"PF-06730512, a promising candidate for the treatment of podocyte injuries. Live at #KidneyWk" (@Cortellis)

Development of a Cell-Based Assay for the Detection of Neutralizing Antibodies to PF-06730512 Using Homogenous Time-Resolved Fluorescence. (PubMed, AAPS J) - "Herein, we describe the development of the assay with a focus on the challenges faced, including drug and blood collection tube interferences in NAb detection. The outcome of our efforts was a robust assay capable of detecting 1 μg/mL of a NAb positive control in the presence of clinically relevant drug concentrations up to 30 μg/mL."

Journal • Preclinical

A Study to Evaluate PF-06730512 in Adults With Focal Segmental Glomerulosclerosis (FSGS) (clinicaltrials.gov) - P2; N=44; Recruiting; Sponsor: Pfizer; Trial completion date: Mar 2021 ➔ Jan 2023; Trial primary completion date: Mar 2021 ➔ Jan 2023

Clinical • Trial completion date • Trial primary completion date

Trial To Evaluate PF-06730512 In Adults With Primary Focal Segmental Glomerulosclerosis (clinicaltrials.gov) - P2; N=44; Recruiting; Sponsor: Pfizer; Trial completion date: Jul 2021 ➔ Mar 2021; Trial primary completion date: Jul 2021 ➔ Mar 2021

Clinical • Trial completion date • Trial primary completion date