VIS171 / Otsuka - LARVOL DELTA

Selective Impact on Regulatory T cell with Sustained Functional Phenotype by the IL-2 Mutein VIS171 in a Nonhuman Primate Model. (PubMed, Am J Transplant) - "Differentiation signature scores indicated preserved Treg functionality following expansion. These findings suggest that VIS171 with rapamycin promotes robust, selective, and durable Treg expansion, offering a strategy to enhance transplant tolerance without broad immunosuppression."

Journal • Preclinical • Transplantation • CD4 • FOXP3 • IL2 • IL2RA • IL7R • ISG20 • TIGIT

An IL-2 Mutein (VIS171) Induces Regulatory T Cells and Prolongs Survival in a Rhesus Kidney Transplant Model (WTC 2025) - "The mIL-2 VIS171, combined with rapamycin, significantly improved graft survival and selectively expanded Tregs in a rhesus macaque kidney transplant model. The distinct peaks of Treg expansion, including the peak increase coinciding with antigen exposure, highlight the potential of VIS171 as an effective strategy for enhancing immune regulation and prolonging allograft survival."

Immune Modulation • Immunology • Transplantation • CD4 • CD8 • FOXP3 • IL2 • IL2RA • ISG20

Selective Enrichment and Functional Preservation of Treg Cells during IL-2 Mutein-Mediated Expansion and Contraction (WTC 2025) - "All three clusters, representing resting, activated, and exhausted regulatory T cell populations, were significantly expanded by VIS171 under rapamycin treatment in rhesus monkeys. Following contraction, Treg cells retained their functional gene profiles, with the activated Treg (HACD4-Treg) populations remaining dominant. These findings suggest that VIS171-mediated Treg expansion does not induce exhaustion but rather preserves their functional capacity."

Transplant Rejection • CD4 • CD8 • IL2 • TIGIT

A Phase 1 Trial to Evaluate the Safety, Tolerability, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of VIS171 in Participants With Autoimmune Disease(s) (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Alopecia • Dermatology • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Study to Evaluate the Safety, PK and PD of VIS171 in Participants (Healthy and with Autoimmune Disease) (clinicaltrials.gov) - P1 | N=61 | Completed | Sponsor: Visterra, Inc. | Terminated ➔ Completed

Trial completion • Immunology

A Phase 1 Trial to Evaluate the Safety, Tolerability, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of VIS171 in Participants With Autoimmune Disease(s) (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

New P1 trial • Alopecia • Dermatology • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Modified-IL-2 (VIS171) to Preferentially Induce Regulatory T Cells in Nonhuman Primates (ATC 2024) - "VIS171 in combination with rapamycin promoted significant and dose dependent Treg expansion post-treatment without impact on CTLs. The pharmacological profile of this novel mIL-2 may have utility in the transplant setting promoting transplant tolerance."

Transplant Rejection • Transplantation • CD4 • CD8 • FOXP3 • IL2 • IL2RA • IL7R • ISG20

A Study to Evaluate the Safety, PK and PD of VIS171 in Participants (Healthy and With Autoimmune Disease) (clinicaltrials.gov) - P1 | N=61 | Terminated | Sponsor: Visterra, Inc. | Trial completion date: Sep 2024 ➔ Feb 2024 | Recruiting ➔ Terminated; The study terminated due to internal strategy change due to changes in risk-benefit ratio

Trial completion date • Trial termination • Immunology

A Study to Evaluate the Safety, PK and PD of VIS171 in Participants (Healthy and With Autoimmune Disease) (clinicaltrials.gov) - P1 | N=76 | Recruiting | Sponsor: Visterra, Inc. | Trial completion date: Jun 2024 ➔ Sep 2024

Trial completion date • Immunology

A Study to Evaluate the Safety, PK and PD of VIS171 in Participants (Healthy and With Autoimmune Disease) (clinicaltrials.gov) - P1 | N=76 | Recruiting | Sponsor: Visterra, Inc.

New P1 trial • Immunology