Antova (ruplizumab) / Biogen - LARVOL DELTA

Mechanistic blockade of Pseudomonas aeruginosa type III secretion by a monoclonal antibody targeting the pore size-determining domain of PcrV. (PubMed, Antimicrob Agents Chemother) - "Humanized Hu5C8 retained potency (KD = 0.55 nM) with extended half-life (t1/2 = 91.26 h) through Fc receptor engineering. As an inhibitor targeting the pore size-determining domain of PcrV, 5C8 disrupts virulence through a novel dual mechanism, providing a paradigm-shifting strategy against multidrug-resistant P. aeruginosa, bridging a critical gap in sepsis management."

Journal • Infectious Disease • Septic Shock • IL6

Graft Survival and Rejection Risk with TNX-1500 as Monotherapy or in Combination with Conventional IS Agents in Nonhuman Primate Heart Transplants (WTC 2025) - "*Purpose: TNX-1500 (TNX) is a humanized IgG4 αCD154 mAb engineered to down-modulate FcγR2 binding to reduce the thromboembolism risk associated with ruplizumab (hu5c8 IgG1). Here in a NHP allo heart transplant model we report an expanded series of weekly dose TNX therapy (Rx), alone (monoRx) or in combination with mycophenolate mofetil (MMF), Rapamycin (Rapa), or Tacrolimus (Tac).* TNX was evaluated as mono Rx (30mg/kg 2x/wk x2, then 20mg/kg/wk; n=19) and combined with TNX+MMF (200 mg/d PO; n=4), TNX+Rapa (target trough 5-10 ng/ml; n=13), or TNX+Tac (target trough 3-5 ng/ml; n=7)... TNX-1500 demonstrated robust efficacy to prevent graft rejection during treatment in NHP, both as monoRx and in combination with conventional immunosuppressive agents. Notably, TNX+Rapa provided superior protection from CAV scores in the later post-Tx intervals. The absence of thromboembolic events predicts safety in clinical translation."

Combination therapy • Monotherapy • Anemia • Cardiovascular • Hematological Disorders • Transplant Rejection • Transplantation

Dual Blockade of CD154 and CD28 Co-Stimulation Pathways Mitigates Pathogenic Allo-Immunity and Enhances Survival in Cynomolgus Cardiac Transplantation (WTC 2025) - "*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... The dual blockade of CD154 and CD28 co-stimulation pathways confers durable protection against pathogenic allo immunity in this stringent preclinical model, suggesting its potential for clinical translation."

Cardiovascular • Hematological Disorders • Hematological Malignancies • Lymphoma • Thrombosis • Transplantation • CD40LG • CTLA4

Extended Survival of 9- and 10-Gene-Edited Pig Heart Xenografts with Ischemia Minimization and CD154 Costimulation Blockade-Based Immunosuppression (Quick-Shot) (ACS-CLINCON 2024) - "Induction with ATG and αCD20 was followed by αCD154 [Tonix] or [primatized hu5c8], MMF, and tapered corticosteroid... Relative to reference genetics without thrombo-regulatory and anti-inflammatory gene expression, 9- or 10-GE pig hearts exhibit promising performance in the context of a clinically applicable regimen including ischemia minimization and αCD154-base IS, justifying further evaluation in an orthotopic model."

Antibody-mediated Rejection • Cardiovascular • CD20 • CD40LG

Extended Survival of 9- and 10-Gene-Edited Pig Heart Xenografts with Ischemia Minimization and CD154 Costimulation Blockade-Based Immunosuppression (ATC 2024) - "Induction with ATG (5mg/kg on d-3 and -1) and αCD20 (20mg/kg on d-1, d0) was followed by αCD154 [Tonix Pharmaceuticals, Chatham, NJ] or primatized hu5c8 [NHPRRC, Boston, MA]; 20mg/kg/wk x6 mo, then 10 mg/kg/wk), MMF (40mg/kg/d), and tapered corticosteroid...IV heparin was given for the first 8-10 days.* Two of the 3-GE grafts functioned well initially but failed within 5 days, with graft necrosis and rupture associated with complement deposition, intravascular thrombi, and myocardial infarction, while the third failed intraoperatively with refractory ventricular fibrillation... Relative to reference genetics without thrombo-regulatory and anti-inflammatory gene expression, 9- or 10-GE pig hearts exhibit promising performance in the context of a clinically applicable regimen including ischemia minimization and αCD154-base IS, justifying further evaluation in an orthotopic model."

Antibody-mediated Rejection • Cardiovascular • Myocardial Infarction • Transplantation • CD20 • CD40LG

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

TNX-1500, an Fc-modified Anti-CD154 Antibody, Prolongs Nonhuman Primate Renal Allograft Survival. (PubMed, Am J Transplant) - "To prevent thromboembolic complications, an IgG4 anti-CD154 mAb, TNX-1500, which retains the Fab antigen binding region of ruplizumab (humanized 5c8, BG9588) was modified by protein engineering to decrease Fc binding to FcγRIIa while retaining certain other effector functions and pharmacokinetics comparable to natural antibodies. Here we report that TNX-1500 treatment is not associated with platelet activation in vitro and consistently inhibits kidney allograft rejection in vivo without clinical or histologic evidence of prothrombotic phenomena. We conclude that TNX-1500 retains efficacy similar to 5c8 to prevent kidney allograft rejection while avoiding previously identified pathway-associated thromboembolic complications."

Journal • Cardiovascular • Immune Modulation • Transplant Rejection • CD40 • CD40LG

Extended Survival of 9- and 10-Gene-Edited Pig Heart Xenografts with Ischemia Minimization and CD154 Costimulation Blockade-Based Immunosuppression (IPITA-IXA-CTRMS 2023) - "Induction with ATG (5mg/kg on d-3 and -1) and aCD20 (20mg/kg on d-1, d0) was followed by aCD154 [Tonix Pharmaceuticals, Chatham, NJ] or primatized hu5c8 [NHPRRC, Boston, MA]; 20mg/kg/wk x6 mo, then 10 mg/kg/wk), MMF (40mg/kg/d), and tapered corticosteroid...IV heparin was given for the first 8-10 days... Relative to reference genetics without thrombo-regulatory and anti-inflammatory gene expression, 9- or 10-GE pig hearts exhibit promising performance in the context of a clinically applicable regimen including ischemia minimization and aCD154-base IS, justifying further evaluation in an orthotopic model. We acknowledge Revivicor and the National Swine Resource and Research Center for providing swine for research purposes. We acknowledge Tonix Pharmaceuticals for providing their pharmaceutical drugs for research purposes."

Antibody-mediated Rejection • Cardiovascular • Myocardial Infarction • Transplantation • CD20 • CD40LG • CD46 • CD55 • PROCR

Efficacy of CD154 Blockade with TNX-1500 to Prevent Heart Allograft Immune Injury (ATC 2023) - "TNX-1500 (‘TNX’) is an Fc-modified IgG4 anti-CD154 monoclonal antibody designed to avoid the thromboembolic complications associated with ruplizumab, an IgG1 with the same Fab binding region...8 of 25 additionally were treated with MMF (40 mg/kg/d; n=4) or rapamycin (Rapa; trough target 5-10ng/ml; n=4) until EOS at d180... TNX monotherapy is well tolerated and usually (14/17) suppresses the pathogenic immune response to a cardiac allograft sufficiently to prevent graft rejection. While both adjuvant agents prevented graft loss, only Rapa co-treatment consistently prevented histologic evidence of graft injury."

Clinical • Anemia • Cardiovascular • Hematological Disorders • Inflammation • Transplant Rejection • Transplantation • CD40LG

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

TNX-1500, an Fc-modified Anti-CD154 Antibody, Prolongs Nonhuman Primate Cardiac Allograft Survival. (PubMed, Am J Transplant) - "Recipients were treated for six months with standard-dose TNX (sTNX) monotherapy, low-dose monotherapy (loTNX), or loTNX with mycophenolate mofetil (loTNX+MMF). Results were compared to historical data using chimeric hu5c8 monotherapy dosed as for loTNX but discontinued at 3 months...No thrombotic complications were observed. This study demonstrates that TNX-1500 was well tolerated, prolongs allograft survival and prevents alloAb production and cardiac allograft vasculopathy in a stringent preclinical NHP heart allo transplant model."

Journal • Cardiovascular • Hematological Disorders • Immune Modulation • Solid Organ Transplantation • Thrombosis • Transplant Rejection • Transplantation • CD40 • CD40LG

TNX-1500, an Fc-Modified Anti-cd154 Antibody, Prolongs Nonhuman Primate Cardiac Allograft Survival (ATC 2022) - "* Cynomolgus monkey heterotopic cardiac allograft recipients were treated with TNX either using a ‘standard’ regimen (sTNX; 30 mg/kg iv twice weekly x4, then 20 mg/kg weekly from d21-180, n=5), using a reduced-dose TNX maintenance regimen (loTNX; 30 mg/kg iv twice weekly x4, 10 mg/kg weekly x6, then 20 mg/kg monthly; n=4), or loTNX with mycophenolate mofetil (loTNX+MMF, 200mg/d po, n=4). Blockade of CD154 with TNX monotherapy is well tolerated and consistently prevents pathologic alloimmunity in this stringent preclinical model at least as effectively as hu5c8 monotherapy. Lower TNX maintenance dosing, with or without MMF, was less effective."

Antibody-mediated Rejection • Cardiovascular • Hematological Disorders • Immune Modulation • Infectious Disease • Inflammation • Thrombocytopenia • Thrombosis • CD40 • CD40LG