Slide 1: TNX-1500, an Fc-modified Anti-CD154 Antibody, Prolongs Nonhuman Primate Cardiac Allograft Survival
TNX - 1500, an Fc - modified Anti - CD154 Antibody, Prolongs Nonhuman Primate Cardiac Allograft Survival Shuhei Miura 1 , Zahra H. Abady 1 , Franziska Pollok 1 , Madelyn Ma 1 , Kohei Kinoshita 1 , Siobhan Fogarty 2 , Patrick Maguire 2 , Bruce Daugherty 2 , Seth Lederman 2 , Richard N. Pierson III 1
Slide 2: Disclosures
Shuhei Miura, MD, Research fellow Center for Transplantation Sciences, Massachusetts General Hospital, Boston MA I have no financial relationships with commercial interests to disclose AND My presentation does not include discussion of off - label or investigational use. SF, BD and SL are Tonix empl
Slide 3: Background: TNX-1500, a novel Fc-modified anti-CD154 mAb
Background TNX - 1500,* a novel Fc - Modified - anti CD154 mAb • The development of humanized 5c8 (ruplizumab) was halted due to thrombotic complications seen in human clinical trials, associated with anti - CD154 Abs to an Fcγ receptor - binding. • Several Abs engineered to down - modulate FcγR - b
Slide 4: Methods: Treatment Groups
Treatment Group Low - dose TNX - 1500 monotherapy (loTNX regimen, n=4) Low - dose TNX - 1500 + MMF (loTNX+MMF regimen, n=4) Protocol biopsies : POD 45 and 90 Methods Heterotopic abdominal allo - heart Tx EOS : POD 180 Group - 1 : Group - 2 : Group - 3 : Control : hu5c8 monotherapy (Reference regimen
Slide 5: Allograft Survival
Results - 1 Allograft Survival Treatment Group MST (range) hu5c8 133 days (90 - 173) loTNX 99 days (35 - 183) loTNX + MMF 88 days (58 - 146) sTNX >265 days (116 - 305) Explant of beating graft Rejection after cessation of sTNX treatment P<0.05 for all comparisons against sTNX
Slide 6: Anti-donor alloantibody elaboration
Results - 2 Anti - donor - alloantibody elaboration loTNX (n=4) loTNX + MMF (n=4) sTNX (n=5)
Slide 7: Results: Representative cardiac pathology at explant
LoTNX monotherapy Day 111 Day 181 LoTNX + MMF sTNX monotherapy Day 93 A B C D E F H&E (x20) H&E (x10) H&E (x20) C4d (x20) Results - 3 Representative cardiac pathology at explant
Slide 8: Platelet counts
Results - 4 Platelet counts No thromboembolic complications were observed.
Slide 9: ISHLT scores and CAV severity scores
Results - 5 ISHLT scores CAV severity scores
Slide 10: Conclusion
Conclusion • Blockade of CD154 with TNX - 1500 monotherapy consistently and safely prevented pathologic alloimmunity in a NHP cardiac allograft model at least as effectively as hu5c8 monotherapy, without clinical thrombotic events. • "Standard - dose” TNX - 1500 regimen was associated with prolonged