Slide 1: Long-Term (>1 year) Rejection Free Survival of Kidney Xenografts in Cynomolgus Monkeys
Long - Term (>1 year) Rejection Free Survival of Kidney Xenografts with Triple Xenoantigen Knockout and Multiple Human Transgenes in Cynomolgus Monkeys Grace Lassiter, MD Background • Triple xeno-antigen knock out (TKO) pigsareexpected to be optimaldonorsfor humanxenotransplantation due to reduced a
Slide 2: Background – Xenotransplantation Barriers & Strategies to Overcome
Background – Xenotransplantation Barriers & Strategies to Overcome • Xenotransplantation has three major barriers to overcome prior to making it clinically available – Hyperacute Rejection (overcome by deletion of 3 carbohydrate xenoantigens ) – Longevity/Chronic Rejection – Zoonotic crossover • Usi
Slide 3: Immunosuppressive Regimen
- 5 - 1 0 30 60 120 180 days Kidney Txp Anti - rhesus Thymocyte Globulin 5mg/kg Anti - CD20 mAb 20mg/kg Solumedrol Tac / Rapa MMF 200 mg PO daily Anti - CD154 mAb (5c8)* 20mg/kg IV every 1 - 2 weeks Immunosuppressive Regimen *Combination of NHPs treated with hu5c8 and TNX - 1500. TNX - 1500 is an in
Slide 4: Summary - Clinical Results
Summary - Clinical Results Group Donor Immunosuppression Survival Days Maintenance Tac/Rapa (1 - 2 months) TKO N=4 aCD154, MMF Tac 50, 6, 4 A EGEN - 2528 (N=2) aCD154, MMF 1 none/ 1 Rapa 61, 2 B EGEN - 2536 (N=6) aCD154, MMF 4 Rapa 265, 71, 20, 15 2 Tac 316, 135 C EGEN - 2734/2784 (N=15) aCD154, MMF
Slide 5: Kaplan-Meier Curve, Kidney Xenograft Survival
Kaplan - Meier Curve, Group C has Median survival of 176 days 0 200 400 600 800 0 50 100 Days post Transplanst P r o b a b i l i t y o f S u r v i v a l Kidney Xenograft Survival Curve Group A Group B Group C Group D TKO (RI)
Slide 6: Group A Group B Group C Group D
GroupA Group B Group C Group D — = on am ey com ann re a compere SD exgtomn ene Proteins: Proteins. ar Proteins Aes es Gee
Slide 7: Conclusion
Conclusion • We consider human transgene insertion to be critical for longterm success of xenotransplantation of kidneys • The role of specific human transgenes, including THBD and EPCR, in preventing xenograft rejection remains to be defined by longer - term observation in more recipients
Slide 8: Acknowledgement
Acknowledgement eGenesis • Michael Curtis, PhD • Chaille Proksch, MPH • Luis M. Queiroz, DVM • Michele E. Youd, PhD • Katherine C. Hall, PhD • Kathryn Stiede, BS • Ian Kohnle , BS • Ellie Tan, BS • Violette B. Paragas , BS • Ranjith Anand, PhD • Jacob Layer, PhD • Yinan Kan, PhD • Wenning Qin, PhD M