Talaris Therapeutics, Inc., (NASDAQ:TALS), a late-clinical stage cell therapy company, today presented a new analysis of HLA mismatching between donors and recipients participating in the Company's Phase 2 trial in
Talaris Therapeutics, Inc., (NASDAQ:TALS), a late-clinical stage cell therapy company, today presented a new analysis of HLA mismatching between donors and recipients participating in the Company's Phase 2 trial in living donor kidney transplant (LDKT). High-resolution allele typing at six loci found that FCR001 induced durable immune tolerance in highly mismatched related and unrelated recipients. The findings were shared in an oral presentation by Joseph R. Leventhal, M.D., Ph.D., Fowler McCormick Professor of Surgery at Northwestern University Feinberg School of Medicine and principal investigator for the Phase 2 study, at the American Society of Hematology (ASH) Annual Meeting.
The new analysis is based on DNA samples collected in Talaris' Phase 2 trial of FCR001 in living donor kidney transplant recipients. The focus of the analysis was to evaluate the degree of donor/recipient HLA mismatching using high-resolution allele typing at HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1, and to understand its correlation with the ability to establish durable chimerism in this patient sample.
Samples from 29 of the 37 donor/recipient pairs were evaluated across all 12 of the relevant HLA alleles; three other donor/recipient pairs were evaluated across 10 alleles as the samples did not have sufficient DNA to test for locus DPB1. In the former group, 21 of 29 donor/recipient pairs had 6/12 or more mismatching; in the latter group, two of the three pairs had 5/10 or more mismatching. Despite this high degree of mismatch, durable chimerism induced by FCR001 allowed for full withdrawal of immunosuppression (IS) in 25 of these 32 subjects, with time off IS ranging from 3.5 to 11 years. Twelve of these 25 pairs were unrelated with ≥ 8 HLA mismatches, and the majority of treated patients showed >95% donor whole blood/T cell chimerism. As previously reported, there was limited incidence of GvHD, being two cases, both in the setting of a female donor to unrelated male recipient. An exclusion criterion for this donor-recipient pairing was added to the Phase 2 trial.
"We're pleased to share this new, more detailed examination of the HLA mismatching among patients in our Phase 2 trial, indicating that FCR001 induced durable immune tolerance across very high levels of mismatch," said Nancy Krieger, M.D., Chief Medical Officer of Talaris. "These insights are highly valuable as we progress our ongoing Phase 3 registrational study in LDKT, FREEDOM-1, and as we continue to expand the applications of Facilitated Allo-HSCT Therapy to other areas of high patient need."