pegrizeprument (FR104) / OSE Immunotherapeutics, Asahi Kasei - LARVOL DELTA

Veloxis Pharmaceuticals Receives Approval from USAN for "Pegrizeprument" as Nonproprietary Name for VEL-101 (PRNewswire) - "Veloxis Pharmaceuticals...has announced that the United States Adopted Name (USAN) Council has approved the nonproprietary (generic) name 'pegrizeprument' for its lead transplant candidate, VEL-101, a novel investigational maintenance immunosuppressive agent....Adopting pegrizeprument ensures consistent and reliable drug identification, helping reduce medication errors, enhance patient safety, and streamline drug identification for healthcare providers. This new generic name also highlights the importance of international drug recognition – ensuring clarity across markets regardless of the brand name under which the drug is intended to be marketed."

Commercial • Transplantation

Costimulation blockade: the next generation. (PubMed, Curr Opin Organ Transplant) - "The focus in transplantation is shifting toward safer, long-term therapies with greater accessibility. Investigational agents with subcutaneous delivery methods could overcome logistical challenges, improve adherence, and redefine posttransplant care. These advancements in costimulation blockade may enhance long-term graft survival and transform the management of KT recipients."

Journal • Cardiovascular • Transplantation • CD40LG

Phase I/II Study of FR104 First Administration in Patient with Renal Transplantation: FIRsT Study (clinicaltrials.gov) - P1/2 | N=10 | Active, not recruiting | Sponsor: Nantes University Hospital | Trial primary completion date: Mar 2024 ➔ Mar 2025

Trial primary completion date • Nephrology • Transplantation

OSE Immunotherapeutics and Nantes University Hospital Present Positive Phase 1/2 Study Evaluating FR104/VEL-101 Immunotherapy in Renal Transplant (GlobeNewswire) - "A total of three oral presentations on FR104/VEL-101 were presented at this congress....featured the results from the Company’s Phase 1 dose escalation clinical trial evaluating the safety, tolerability, pharmacodynamics and pharmacokinetics of single ascending doses of subcutaneous administration of FR104/VEL-101 in healthy participants. A third oral communication...reported on the positive preclinical efficacy data of FR104/VEL-101 injection in monotherapy or in combination with anti-CD40L antibody to protect from acute and chronic heart allograft rejection."

P1 data • Preclinical • Immunology • Transplant Rejection

OSE Immunotherapeutics and Nantes University Hospital Present Positive Phase 1/2 Study Evaluating FR104/VEL-101 Immunotherapy in Renal Transplant (GlobeNewswire) - P1/2 | N=10 | FIRsT (NCT04837092) | "We are very pleased to share the positive results of the FIRsT study at international congress on post-transplant immune response and one-year safety in patients treated with FR104/VEL-101....'The data presented show the safety of the product used in combination and the first signs of efficacy in kidney transplant recipients with no episodes of acute rejection after one year follow-up in all patients of the study. The exploration of FR104/VEL-101’s safety profile seems promising and encourages moving to a Phase 2 trial for patients undergoing renal transplant who require innovative solution.'...No safety alert was detected for FR104/VEL-101....With a follow-up of 1 year in all patients, not only no acute rejection under FR104/VEL-101 was observed, and notably no acute rejection episodes occurred after discontinuation of tacrolimus, but also no immunization against the donor occurred."

P1/2 data • Immunology • Transplant Rejection • Transplantation

Veloxis Pharmaceuticals Selected to Present at the 2024 American Transplant Congress in Philadelphia (PRNewswire) - "Veloxis Pharmaceuticals...is pleased to announce the presentation of VEL-101 research at the 2024 American Transplant Congress (ATC). VEL-101 (also known as FR104) is a novel investigational maintenance immunosuppressive agent being developed for prevention of acute rejection in kidney transplant recipients...The presentation will include data from a Veloxis-sponsored Phase 1 dose escalation study in healthy participants evaluating safety and pharmacokinetics of VEL-101 following intravenous and SQ administration, presented by Dr. Simon Tremblay, Senior Director of Clinical Development and Clinical Development Lead for VEL-101 at Veloxis....a Phase 1/2 clinical trial in kidney transplant recipients, will be presented by Professor Gilles Blancho..."

P1 data • P1/2 data • Transplant Rejection • Transplantation

Combined Blockade of the CD154 and CD28 Co-Stimulation Pathways Attenuates Pathogenic Alloimmunity and Prolongs Survival in Cynomolgus Cardiac Allografts (ATC 2024) - "*Purpose: TNX-1500 (TNX) is a novel humanized αCD154 mAb that contains the hu5c8 Fab region and an IgG4 Fc region engineered to modulate FcγR2 binding to reduce the risk of thromboembolic events seen with ruplizumab (hu5c8 IgG1) in previous clinical trials... Combined blockade of the CD154 and CD28 co-stimulation pathways is associated with durable protection from pathogenic alloimmunity in this stringent model, suggesting a promising approach for clinical translation."

Cardiovascular • Hematological Disorders • Thrombosis • CD40LG

Safety, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Fixed-Dose, Subcutaneous (SQ) Administration of VEL-101, an Anti-CD28 Pegylated Monoclonal Antibody Fragment, in Healthy Participants (ATC 2024) - P1 | "*Purpose: VEL-101, also known as FR104, is a monovalent, humanized anti-CD28 PEGylated monoclonal antibody fragment that selectively blocks CD28 co-stimulation, while sparing CTLA-4 inhibition... IP administration was generally well tolerated, and SQ administration of VEL-101 resulted in serum concentrations yielding detectable CD28 RO at levels compatible for future study in kidney transplant recipients."

Clinical • PK/PD data • Pain • Transplantation

Phase I/II Study of FR104 First Administration In Patient With Renal Transplantation: FIRsT Study (clinicaltrials.gov) - P1/2 | N=10 | Active, not recruiting | Sponsor: Nantes University Hospital

Trial completion date • Trial primary completion date • Nephrology • Transplantation

Phase I/II Study of FR104 First Administration In Patient With Renal Transplantation: FIRsT Study (clinicaltrials.gov) - P1/2 | N=10 | Active, not recruiting | Sponsor: Nantes University Hospital | Recruiting ➔ Active, not recruiting

Enrollment closed • Nephrology • Transplantation

OSE Immunotherapeutics and Nantes University Hospital Announce Completion of Patient Enrollment in the FIRsT Clinical Trial, a Phase 1/2 Study Evaluating FR104/VEL-101 Immunotherapy in Renal Transplantation (Businesswire) - "OSE Immunotherapeutics SA...and Nantes University Hospital announced today the completion of patient enrollment in the FIRsT Study. This Phase 1/2 clinical trial is the first study to evaluate the immunotherapy FR104/VEL-101...in patients undergoing renal transplant. This study is sponsored and conducted by the University Hospital of Nantes as part of a collaboration agreement with OSE Immunotherapeutics."

Enrollment closed • Immunology • Solid Organ Transplantation

aCD154mAb (TNX-1500) Alone or with Rapamycin, MMF, aCD28mAb (VEL-101) Prolongs Cynomolgus Cardiac Allograft Survival [Board No. A030] (ATC 2023) - "Purpose: TNX-1500 (TNX) is a novel humanized αCD154 mAb that contains the hu5c8 Fab region and an IgG4 Fc region engineered to modulate FcγR2 binding to reduce the risk of thromboembolic events seen with hu5c8 IgG1 in previous clinical trials...loTNX monotherapy (n=4) was evaluated with additional treatment with either mycophenolate mofetil (loTNX+MMF, n=4) or VEL-101, αCD28 PEGylated monovalent Fab (loTNX+VEL-101, n=3)... stTNX is associated with durable protection from pathogenic alloimmunity; stTNX+Rapa significantly inhibits pathogenic alloimmunity relative to stTNX or stTNX+MMF, suggesting one promising approach for clinical translation."

Cardiovascular • Hematological Disorders • Infectious Disease • Thrombocytopenia • Thrombosis

A Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VEL-101 (clinicaltrials.gov) - P1 | N=60 | Completed | Sponsor: Veloxis Pharmaceuticals | Recruiting ➔ Completed

Trial completion • CRP • IFNG • IL10 • IL17A • IL1B • IL2 • IL6 • TNFA

A Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VEL-101 (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Veloxis Pharmaceuticals | Trial completion date: Oct 2022 ➔ Jan 2023 | Trial primary completion date: Aug 2022 ➔ Jan 2023

Trial completion date • Trial primary completion date • CRP • IFNG • IL10 • IL17A • IL1B • IL2 • IL6 • TNFA

OSE Immunotherapeutics Announces Corporate Update and H1 2022 Results (Businesswire) - "A newly formed SAB combining the expertise of renowned scientific and international key-opinion leaders in the fields of immunology, immuno-oncology, inflammation and immunotherapy...The SAB includes...Dr. Jennifer Wargo...."

A Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VEL-101 (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: Veloxis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • CRP • IFNG • IL10 • IL17A • IL1B • IL2 • IL6 • TNFA

Phase I/II Study of FR104 First Administration In Patient With Renal Transplantation: FIRsT Study (clinicaltrials.gov) - P1/2 | N=10 | Recruiting | Sponsor: Nantes University Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Nephrology • Transplantation

A Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VEL-101 (clinicaltrials.gov) - P1 | N=56 | Not yet recruiting | Sponsor: Veloxis Pharmaceuticals | Trial completion date: Jul 2022 ➔ Oct 2022 | Trial primary completion date: May 2022 ➔ Aug 2022

Trial completion date • Trial primary completion date • CRP • IFNG • IL10 • IL17A • IL1B • IL2 • IL6 • TNFA

OSE Immunotherapeutics and Veloxis Pharmaceuticals Enter Into Global License Agreement to Develop, Manufacture, and Commercialize FR104, a CD28 Antagonist, in the Organ Transplantation Market (Businesswire) - "OSE Immunotherapeutics...and Veloxis Pharmaceuticals...today announced a global license agreement granting Veloxis Pharmaceuticals worldwide rights to develop, manufacture and commercialize FR104...Through this license agreement, Veloxis plans to develop FR104 to provide a new therapeutic option for prophylaxis of organ rejection in patients receiving a solid organ transplant....OSE Immunotherapeutics will receive up to €315 million in potential milestones from Veloxis, including a €7 million upfront payment...Veloxis will assume all production, development and commercialization costs in the transplant indications for FR104..."

Licensing / partnership • Graft versus Host Disease

Phase I/II Study of FR104 First Administration In Patient With Renal Transplantation: FIRsT Study (clinicaltrials.gov) - P1/2; N=10; Not yet recruiting; Sponsor: Nantes University Hospital

New P1/2 trial • Nephrology • Renal Disease • Transplantation

OSE Immunotherapeutics Enters a Loan Agreement of up to €25 Million with the European Investment Bank (GlobeNewswire) - “OSE Immunotherapeutics SA...today announced hat the Company has signed a loan agreement of up to €25 million with the European Investment Bank (EIB)....The remaining two tranches of €10 and €5 million, available upon achievement of specific clinical milestones, are planned to be used to accelerate the clinical development of the Company’s other programs, in particular CD28 antagonist FR104…”

Financing • Graft versus Host Disease • Immunology

OSE Immunotherapeutics Receives European Patent Notice of Allowance for First-in-Class CD28-Antagonist Immunotherapy FR104 (GlobeNewswire) - "OSE Immunotherapeutics...announced the European Patent Office’s (EPO) issuance of a notice of allowance for its Phase-2 ready product FR104...this European patent will provide additional protection covering novel dosing regimen of FR104 for the prevention and treatment of T-lymphocyte-mediated autoimmune diseases, inflammatory diseases, transplantation and graft-versus-host disease (GVHD) until 2036."

Patent • Graft versus Host Disease • Immunology • Inflammation

OSE Pharma and Effimune announce proposed merger to create significant immunotherapy player (Businesswire) - "At the end of 2013, with FR104 at a preclinical stage, a global option and license agreement was signed with Janssen Biotech...which allowed the development of the product to this stage. This option could be exercised by Johnson & Johnson in the second half of 2016 to continue Phase 2 clinical development, with expected payments of milestones and royalties."

Pipeline update • Inflammation

Preemptive B Cell Depletion Modulates Pathogenic Alloimmunity Associated with Selective Non-Activating CD28 Blockade (ATC 2018) - "...Here, we evaluate an αCD20 agent specifically developed for use in non-human primates to evaluate preemptive B cell depletion in the context of selective αCD28 blockade. Cynomolgus monkey MHC-mismatched heterotopic cardiac allograft transplant recipients were treated for 3 months with a selective non-activating αCD28 (FR104, n=12)... Efficient, durable preemptive B cell depletion using RhαCD20 prevents graft rejection during αCD28 treatment, as previously shown in this model in conjunction with CsA and αCD154 regimens. Our observations suggest that B cell depletion may also interfere with emergence of graft-protective immunomodulation that develops in some recipients with αCD28 treatment. Both preemptive B cell depletion and selective non-activating αCD28 blockade deserve further evaluation to prevent pathogenic alloimmunity, alloAb elaboration, and chronic allograft vasculopathy."

IO Biomarker • Biosimilar • Graft versus Host Disease • Immune Modulation • Immunology • Inflammation • Ophthalmology • Test

FR104: Initiation of P2 trial for rheumatoid arthritis in 2019 (OSE Immunotherapeutics) - Corporate Overview

New P2 trial