*Purpose: to assess safety, T cell depletion, PK/PD and determine the therapeutic dose of LIS1, a purified anti-lymphocyte glyco-humanized polyclonal swine IgG, derived by immunizing with a human T cell line double Knock-Out swine lacking the two xeno-antigens α-1-3 galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc), thus avoiding serum sickness and the possible systemic inflammation called xenosialitis, LIS1 is “FC-silenced” so that it mediates no antibody-dependent cell-mediated cytotoxicity but strongly activates complement-mediated cytotoxicity. Preclinical studies in non-human primates demonstrated (i) selective depletion of T cells (CD4+ and CD8+) versus myeloid, Treg and B cells, this depletion being more controlled in time as compared to rabbit ALG, and (ii) prevention of skin graft rejection similarly to rabbit ALG.

*Methods: phase Ib, open-label, single site, conducted in two sequential cohorts, Ascending Dose cohort (n=5) and Therapeutic Dose cohort (n=5). LIS1 administered by IV central catheter over 8-12 hours, one daily dose, 5 consecutive days, starting at day 1 post-transplantation, in first kidney transplant patients with PRA < 50%, FCXM-, DSA, EBV+.

*Results: 10 patients were included, 6 men and 4 women, mean PRA 7.8 % (± 12.3), mean age 48,6 years (± 8,7). All received tacrolimus, mycophenolic acid, and steroids, as maintenance therapy. Safety: No platelets depletion, nor related adverse event were observed.

Efficacy:Doses of 0.6; 1 and 3 mg/Kg were suboptimal. Dose of 6 mg/kg resulted in CD3+ T-cell depletion < 100/mm3 at day 2 with recovery within a week. Doses of 8 and 10 mg/Kg resulted in CD3+ T-cell depletion < 100/mm3 at day 2 with recovery within 2 to 4 weeks (see figure).

*Conclusions: LIS1 at a dose of 8-10 mg/kg is safe and well tolerated and allows a controlled-in-time selective depletion of target CD3+ T cells. Phase II multicentric double blind study is planned.

« Back to 2022 American Transplant Congress