A Safety Study of SEA-BCMA in Patients With Multiple Myeloma

Area under the observed concentration-time curve from the time of dosing to Day 14 calculated by log-linear trapezoidal approximation.

Area under the observed concentration-time curve from the time of dosing to Day 7 calculated by log-linear trapezoidal approximation.

Area under the observed concentration-time curve from the time of dosing to Day 7 calculated by log-linear trapezoidal approximation.

Area under the observed concentration-time curve from the time of dosing to Day 7 calculated by log-linear trapezoidal approximation.

Area under the observed concentration-time curve from the time of dosing to Day 7 calculated by log-linear trapezoidal approximation.

A positive baseline ATA result was considered positive post-baseline if the post-baseline ATA titer result was at least four times higher than the baseline result.

A positive baseline ATA result was considered positive post-baseline if the post-baseline ATA titer result was at least four times higher than the baseline result.

A positive baseline ATA result was considered positive post-baseline if the post-baseline ATA titer result was at least four times higher than the baseline result.

A positive baseline ATA result was considered positive post-baseline if the post-baseline ATA titer result was at least four times higher than the baseline result.

ORR: Percentage of participants with an objective response (OR) per investigator. Participant was determined to have an OR if, based on 2016 IMWG uniform response criteria, \& achieved stringent complete response (sCR), Complete response (CR), very good partial response(VGPR) \& partial response(PR): free light chain(FLC) ratio \& absence of clonal cells in bone marrow by immunohistochemistry(IC)/ immunofluorescence(IF). CR: negative immunofixation of serum \& urine, disappearance of any soft tissue plasmacytomas(STP), 5% plasma cells in bone marrow. VGPR: serum \& urine M-protein (UMP) detectable by immunofixation but not on electrophoresis/ >= 90% reduction in serum M-protein (SMP) level+UMP level <100 mg/24 hr, PR: >=50% reduction of SMP \& reduction in 24-hr urinary M-protein by >=90%/to <200 mg/24 hr. If SMP \& UMP are unmeasurable, a ≥50% decrease in the difference between involved \& uninvolved FLC levels were required in place of the M-protein criteria.

The ORR was defined as the percentage of participants with an OR per investigator. A participant was determined to have an OR if, based on the 2016 IMWG uniform response criteria, and achieved a sCR, CR, VGPR, or a PR. sCR: FLC ratio \& absence of clonal cells in bone marrow by IC/IF. CR: negative immunofixation of serum \& urine, disappearance of any STP, 5% plasma cells in bone marrow. VGPR: serum and UMP detectable by immunofixation but not on electrophoresis or >= 90% reduction in SMP level+UMP level <100 mg/24 hour, PR: >=50% reduction of SMP \& reduction in 24-hour urinary M-protein by >=90%/to <200 mg/24 hour. If SMP \& UMP are unmeasurable, a ≥50% decrease in the difference between involved \& uninvolved FLC levels were required in place of the M-protein criteria. In addition to above criteria, if present at baseline, >=50% reduction in the size of STP were also required.

The ORR was defined as the percentage of participants with an OR per investigator. A participant was determined to have an OR if, based on the 2016 IMWG uniform response criteria, and achieved a sCR, CR, VGPR, or a PR. sCR: FLC ratio \& absence of clonal cells in bone marrow by IC/IF. CR: negative immunofixation of serum \& urine, disappearance of any STP, 5% plasma cells in bone marrow. VGPR: serum and UMP detectable by immunofixation but not on electrophoresis or >= 90% reduction in SMP level+UMP level <100 mg/24 hour, PR: >=50% reduction of SMP \& reduction in 24-hour urinary M-protein by >=90%/to <200 mg/24 hour. If SMP \& UMP are unmeasurable, a ≥50% decrease in the difference between involved \& uninvolved FLC levels were required in place of the M-protein criteria. In addition to above criteria, if present at baseline, >=50% reduction in the size of STP were also required.

The ORR was defined as the percentage of participants with an OR per investigator. A participant was determined to have an OR if, based on the 2016 IMWG uniform response criteria, and achieved a sCR, CR, VGPR, or a PR. sCR: FLC ratio \& absence of clonal cells in bone marrow by IC/IF. CR: negative immunofixation of serum \& urine, disappearance of any STP, 5% plasma cells in bone marrow. VGPR: serum and UMP detectable by immunofixation but not on electrophoresis/ >= 90% reduction in SMP level+UMP level <100 mg/24 hour, PR: >=50% reduction of SMP \& reduction in 24-hour urinary M-protein by >=90%/to <200 mg/24 hour. If SMP \& UMP are unmeasurable, a ≥50% decrease in the difference between involved \& uninvolved FLC levels were required in place of the M-protein criteria. In addition to above criteria, if present at baseline, >=50% reduction in the size of STP were also required.

BOR consisted of MRD-negative CR,sCR,CR,VGPR,PR,MR,SD \& PD per 2016 IMWG. MRD: evaluated using adaptive next generation sequencing(NGS) for MRD assay \& carried out on relevant specimen to understand activity of SEA-BCMA. sCR: CR \& normal FLC ratio \& absence of clonal cells in bone marrow by IC/ IF. CR: Negative immunofixation of serum \& urine disappearance of any STP, \& <5% plasma cells in bone marrow. VGPR: SMP \& UMP detectable by IF but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hr, PR: >=50% R of SMP \& R in 24-hr UMP by >=90%/by <200 mg/24 hr. If SMP \& UMP are unmeasurable, >=50% decrease in difference between involved \& uninvolved FLC levels were required in place of M-protein criteria. SD: Not meeting criteria for CR, VGPR, PR, MR, or progression. MR: 25-49% R of SMP \& R in 24-hr UMP by 50-89%, which still exceeds 200mg/24 hr. DP: objective evidence of tumor progression(based on serum/urine/BM assessments) \&/clinical progression/investigator.

BOR consisted of MRD-negative CR, sCR, CR, VGPR, PR, MR, SD \& PD per 2016 IMWG. MRD: evaluated using adaptive NGS for MRD assay \& carried out on relevant specimen to understand activity of SEA-BCMA. sCR: CR \& normal FLC ratio \& absence of clonal cells in bone marrow by IC/ IF. CR: Negative immunofixation of serum \& urine disappearance of any STP, \& <5% plasma cells in bone marrow. VGPR: SMP \& UMP detectable by IF but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hr, PR: >=50% R of SMP \& R in 24-hr UMP by >=90%/by <200 mg/24 hr. If SMP \& UMP are unmeasurable, >=50% decrease in difference between involved \& uninvolved FLC levels were required in place of M-protein criteria. SD: Not meeting criteria for CR, VGPR, PR, MR, or progression. MR: 25-49% R of SMP \& R in 24-hr UMP by 50-89%, which still exceeds 200mg/24 hr. DP: objective evidence of tumor progression(based on serum/urine/BM assessments) \&/clinical progression/investigator.

BOR consisted of MRD-negative CR, sCR, CR, VGPR, PR, MR, SD \& PD per 2016 IMWG. MRD: evaluated using NGS for MRD assay \& carried out on relevant specimen to understand activity of SEA-BCMA. sCR: CR \& normal FLC ratio \& absence of clonal cells in bone marrow by IC/ IF. CR: Negative immunofixation of serum \& urine disappearance of any STP, \& <5% plasma cells in bone marrow. VGPR: SMP \& UMP detectable by IF but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hr, PR: >=50% R of SMP \& R in 24-hr UMP by >=90%/by <200 mg/24 hr. If SMP \& UMP are unmeasurable, >=50% decrease in difference between involved \& uninvolved FLC levels were required in place of M-protein criteria. SD: Not meeting criteria for CR, VGPR, PR, MR, or progression. MR: 25-49% R of SMP \& R in 24-hr UMP by 50-89%, which still exceeds 200mg/24 hr. DP: objective evidence of tumor progression(based on serum/urine/BM assessments) \&/clinical progression/investigator.

BOR consisted of MRD-negative CR,sCR,CR,VGPR,PR,MR,SD \& PD per 2016 IMWG. MRD: evaluated using adaptive NGS for MRD assay \& carried out on relevant specimen to understand activity of SEA-BCMA. sCR: CR \& normal FLC ratio \& absence of clonal cells in bone marrow by IC/ IF. CR: Negative immunofixation of serum \& urine disappearance of any STP, \& <5% plasma cells in bone marrow. VGPR: SMP \& UMP detectable by IF but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hr, PR: >=50% R of SMP \& R in 24-hr UMP by >=90%/by <200 mg/24 hr. If SMP \& UMP are unmeasurable, >=50% decrease in difference between involved \& uninvolved FLC levels were required in place of M-protein criteria. SD: Not meeting criteria for CR, VGPR, PR, MR, or progression. MR: 25-49% R of SMP \& R in 24-hr UMP by 50-89%, which still exceeds 200mg/24 hr. DP: objective evidence of tumor progression(based on serum/urine/BM assessments) \&/clinical progression/investigator.

DOR: Time from first documentation of OR(sCR,CR,VGPR/PR) to first documentation of PD/death due to any cause, whichever came first. PD: Objective evidence of tumor progression(TP) (based on serum, urine/BM assessments) \&/clinical progression/ investigator. sCR: CR, normal FLC ratio \& absence of clonal cells in bone marrow by IC/IF. CR: Negative immunofixation of serum\&urine, disappearance of any STP, \&<5% plasma cells in bone marrow. VGPR: Serum \& UMP detectable by immunofixation but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hour, PR: >=50%R of SMP \& R in 24-hour UMP by >=90% or to <200 mg/24 hour. DOR: censored on date of last disease assessment documenting absence of PD for participants who do not have PD \& were still on study at the time of an analysis/removed from study prior to documentation of TP. Participants started new antitumor treatment prior to documentation of PD were censored at last disease assessment prior to start of new treatment.

DOR: Time from first documentation of OR(sCR,CR,VGPR/PR) to first documentation of PD/death due to any cause, whichever came first. PD: Objective evidence of tumor progression(TP) (based on serum, urine/BM assessments) \&/clinical progression/ investigator. sCR: CR, normal FLC ratio \& absence of clonal cells in bone marrow by IC/IF. CR: Negative immunofixation of serum\&urine, disappearance of any STP, \&<5% plasma cells in bone marrow. VGPR: Serum \& UMP detectable by immunofixation but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hour, PR: >=50%R of SMP \& R in 24-hour UMP by >=90% or to <200 mg/24 hour. DOR: censored on date of last disease assessment documenting absence of PD for participants who do not have PD \& were still on study at the time of an analysis/removed from study prior to documentation of TP. Participants started new antitumor treatment prior to documentation of PD were censored at last disease assessment prior to start of new treatment.

DOR: Time from first documentation of OR(sCR,CR,VGPR/PR) to first documentation of PD/death due to any cause, whichever came first. PD: Objective evidence of tumor progression(TP) (based on serum, urine/BM assessments) \&/clinical progression/ investigator. sCR: CR, normal FLC ratio \& absence of clonal cells in bone marrow by IC/IF. CR: Negative immunofixation of serum\&urine, disappearance of any STP, \&<5% plasma cells in bone marrow. VGPR: Serum \& UMP detectable by immunofixation but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hour, PR: >=50%R of SMP \& R in 24-hour UMP by >=90% or to <200 mg/24 hour. DOR: censored on date of last disease assessment documenting absence of PD for participants who do not have PD \& were still on study at the time of an analysis/removed from study prior to documentation of TP. Participants started new antitumor treatment prior to documentation of PD were censored at last disease assessment prior to start of new treatment.

DOR: Time from first documentation of OR(sCR,CR,VGPR/PR) to first documentation of PD/death due to any cause, whichever came first. PD: Objective evidence of tumor progression(TP) (based on serum, urine/BM assessments) \&/clinical progression/ investigator. sCR: CR, normal FLC ratio \& absence of clonal cells in bone marrow by IC/IF. CR: Negative immunofixation of serum\&urine, disappearance of any STP, \&<5% plasma cells in bone marrow. VGPR: Serum \& UMP detectable by immunofixation but not on electrophoresis/ >= 90% reduction(R) in SMP level+UMP level <100 mg/24 hour, PR: >=50%R of SMP \& R in 24-hour UMP by >=90% or to <200 mg/24 hour. DOR: censored on date of last disease assessment documenting absence of PD for participants who do not have PD \& were still on study at the time of an analysis/removed from study prior to documentation of TP. Participants started new antitumor treatment prior to documentation of PD were censored at last disease assessment prior to start of new treatment.

PFS: Time from the start of any study treatment to first documentation of DP or to death due to any cause, whichever comes first. DP included objective evidence of tumor progression (based on serum, urine or BM assessments) and/or clinical progression per investigator. PFS was censored on the date of the last disease assessment documenting absence of PD for participants who do not have disease progression and are still on study at the time of an analysis, or discontinuation of study prior to documentation of tumor progression. Participants who have started a new antitumor treatment prior to documentation of PD were censored at the last disease assessment prior to start of new treatment. Participants lacking an evaluation of tumor response after their first dose had their event time censored as 1 day.

PFS: Time from the start of any study treatment to first documentation of DP or to death due to any cause, whichever comes first. DP included objective evidence of tumor progression (based on serum, urine or BM assessments) and/or clinical progression per investigator. PFS was censored on the date of the last disease assessment documenting absence of PD for participants who do not have disease progression and are still on study at the time of an analysis, or discontinuation of study prior to documentation of tumor progression. Participants who have started a new antitumor treatment prior to documentation of PD were censored at the last disease assessment prior to start of new treatment. Participants lacking an evaluation of tumor response after their first dose had their event time censored as 1 day.

PFS: Time from the start of any study treatment to first documentation of DP or to death due to any cause, whichever comes first. DP included objective evidence of tumor progression (based on serum, urine or BM assessments) and/or clinical progression per investigator. PFS was censored on the date of the last disease assessment documenting absence of PD for participants who do not have disease progression and are still on study at the time of an analysis, or discontinuation of study prior to documentation of tumor progression. Participants who have started a new antitumor treatment prior to documentation of PD were censored at the last disease assessment prior to start of new treatment. Participants lacking an evaluation of tumor response after their first dose had their event time censored as 1 day.

PFS: Time from the start of any study treatment to first documentation of DP or to death due to any cause, whichever comes first. DP included objective evidence of tumor progression (based on serum, urine or BM assessments) and/or clinical progression per investigator. PFS was censored on the date of the last disease assessment documenting absence of PD for participants who do not have disease progression and are still on study at the time of an analysis, or discontinuation of study prior to documentation of tumor progression. Participants who have started a new antitumor treatment prior to documentation of PD were censored at the last disease assessment prior to start of new treatment. Participants lacking an evaluation of tumor response after their first dose had their event time censored as 1 day.

OS was defined as the time from the start of any study treatment to the date of death due to any cause. OS was calculated as date of death minus date of first dose of any study treatment plus 1. OS for participants who were alive at their date of last contact, including those lost to follow-up, were censored at the date of last contact. If the last recorded date where a participant was known to be alive is the date of first dose of any study treatment, survival time was censored on the date of first dose of any study treatment (i.e., OS duration of 1 day).

OS was defined as the time from the start of any study treatment to the date of death due to any cause. OS was calculated as date of death minus date of first dose of any study treatment plus 1. OS for participants who were alive at their date of last contact, including those lost to follow-up, were censored at the date of last contact. If the last recorded date where a participant was known to be alive is the date of first dose of any study treatment, survival time was censored on the date of first dose of any study treatment (i.e., OS duration of 1 day).

OS was defined as the time from the start of any study treatment to the date of death due to any cause. OS was calculated as date of death minus date of first dose of any study treatment plus 1. OS for participants who were alive at their date of last contact, including those lost to follow-up, were censored at the date of last contact. If the last recorded date where a participant was known to be alive is the date of first dose of any study treatment, survival time was censored on the date of first dose of any study treatment (i.e., OS duration of 1 day).

OS was defined as the time from the start of any study treatment to the date of death due to any cause. OS was calculated as date of death minus date of first dose of any study treatment plus 1. OS for participants who were alive at their date of last contact, including those lost to follow-up, were censored at the date of last contact. If the last recorded date where a participant was known to be alive is the date of first dose of any study treatment, survival time was censored on the date of first dose of any study treatment (i.e., OS duration of 1 day).