[Music] hello everyone um I'm BAGI doara from vanderville University Medical Center in Nashville Tennessee and today I'll be uh reviewing uh our Ash 2023 abstract on pbcm L1 um allogenic kmetic antigen receptor t- cell therapy in patients with relapse refractory multiple Myoma I'll be reviewing some of the early preliminary data from phase one dose escalation cohort of this trial there have been multiple autologous Carol therapy products approved Now by FAA for relap refractory multiple Myoma ho
wever there is still a need for developing newer therapies therapies which we can use quickly um as we know autologous products requires anywhere from 4 to six we of manufacturing and many of our aggressive Progressive Myoma are not able to wait that long um there is also AIS risk of relapse after autologous Cel therapy so pbcm L1 is a nonviral vector Gene edited allogenic Cell Therapy which again targets the same B cell maturation antigen bcma protein on Myoma surface uh antigen so um going ove
r a little bit about the manufacturing of this Cel therapy in healthy donors donated the te- cell and they are Gene edited using this uh proprietary nonviral Vector piggyback Gene insertion and cast Clower Gene editing platform and then multiple batches of CES were manufactured after just leukopheresis from one donor this is overall study schema uh patients with relapse refractory multiple Myoma triple class exposed were enroll uh total um 39 patients were enroll on the study and everybody had C
arol infusion important thing to keep in mind here is that time from enrollment to start of lympho depletion was merely one day uh which is a significant Improvement compared to autologous cart cell products the study has multiple dosing cohort as well as different lympo depletion cohorts early on on the trial we learned that standard lympo depletions with flu arabin and cyclosome uh failed to um be beneficial because most of these patient did not have adequate invivo cartis expansion so enhance
d lympo depletion uh cohort were introduced very early in the trial so arm P1 and P2 has higher doses of cyclophosphomide and we'll learn later on that it does lead to positive impact on the efficacy of the ctis cell little bit about the Baseline characteristics of the treated patient uh these were heavily pre treated patients with median seven prior lines of therapy 39% of the patient has prior bcma targeting therapy such as autologous caral therapy or any other BCM targeting therapy including
teista there were high-risk cytogenetic stereotype in most of the patient uh and the median patient age was 68 years old looking at the initial safety results from this phase one trial no dlts reported at the highest infused dose of 6 million per kilogram uh most importantly this being an allogenic te- cell product we did not see any evidence of graph versus host disease so far on the trial overall incidence of cyto kind release syndrome and immuneffector cell therapy related neurotoxicity or I
can were actually significantly lower compared to what we have seen with other ctis cell product most CRS and Ians events with grade one or two and they were very shortlived patients were treated with tocilizumab and steroid in most of these cases even in higher lymo depletion cohorts we did not reported any serious infections here looking at invivo cell kinetics across the different lymphodepleting cohort looking at the standard lympo depletion very minimal invivo expansion and persistent was s
een however there was a dose dependent Improvement in CTI expansion and area under curve in arm P1 and P2 which included higher doses of cyclophosphomide confirming that this allogenic product does require higher lympo depletion compared to autologous CTI product to be effective uh these cartes expanded well and many of these patient had long-term persistent Beyond month two uh these cells also lead to differentiation in the recipient so majority of the C cell which were infused in the patient w
ith a t- cell memory phenotype but over time as you can see here on the slide these te- cells differentiate into effor t- cell in the patient here in a small cohort of patients looking at efficacy on the multiple Myoma uh the standard LIF for depletion eight patient we did not see much anti-tumor activity however in arm P1 and P2 um significant Improvement in efficacy so overall enhan lympo depletion cohort total 11 patient the response rate was 82% with majority being vgpr or better uh if we ex
clude the patient who had prior BCM therapies the overall response rate was 100% among the five patients who had MD status evaluable two had mrd negative deas at the time of last evaluation so in summary uh pbcm L1 uh is an off-the-shelf allogenic nonviral Vector Gene editing car T Cel therapy targeting bcma in this phase one clinical trial um looking at the safety and early efficacy of this drug in a patient with relapse refractory multiple Myoma we showed that so far there were no DT and no gr
aph versus host disas and overall incidence of CRS neurotoxicity was acceptable um very few great three or grade for infection events even in higher lymphodepletion cohorts um impressive overall response rates were seen in a small cohort of patient so far 11 patient only uh but in enhanced L for depletion 82% overall response rate and few of them had a deep durable remissions um ongoing enrollment um is going on right now and um we'll further report the outcome as it comes thank [Music] you
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