50 µm50 µm 50 µm
0 140
50
100
150
200
0
5000
10000
15000
200005B-5
Days Post-BPX-601
Cells
/mcl BPX-601
(copies/µgD
NA)
Rim
7
0 140
200
400
600
0
10000
20000
300005B-2
Days Post-BPX-601
Cells
/mcl BPX-601
(copies/µgD
NA)
Rim
7
−4 −2 0 2 4
05
10
CXCL10CXCL11IDO1CXCL9GBP4CCL8CCL7IFIT3CCL5GBP1
PSCAEIF5AL1PLA2G2AFGF18NCAM1WNT11TNFRSF11BTNFRSF10CBAMBIEGF
Pa�ent 5B-5
−4 −2 0 2 4
05
10
C5TDO2ARG1HLA-DRB5IL4CXCL13SERPINA1HSDB11B1C2APOE
HLA-DPA1SPP1EROA1CCL3/L1COL17A1IL1BLAMC2MMP1TREM1WNT7B
Pa�ent 5B-4
Average Expression−4 −2 0 2 4
05
10
HLA-DQA1CDC25CHLA-DRB5ICOSOTOAP4HA2IL10CBLCFASLGLAG3
IRF8RUNX3ZAP70NCAM1FGF13PNOCJAG2ARNT2IL34EGF
Pa�ent 5B-2
Log2
FC(P
re/P
ost)G-CSF GM-CSF
IL−17A
IL−1RA
IL−1β
IL−7
IL−8 MCP−1 MIP−1β
TNF-α
VEGF
IFN-γ
IL−10
IL−5
IL−6
IP−10
IL-2
Log(
pg/m
l)-Ba
selin
e
Base
line
Day
0−Pr
eDa
y 0−
1hDa
y 0−
4hDa
y 1
Day
2Da
y 4
Day
7Da
y 7
(Rim
+1 h
)Da
y 7
(Rim
+4 h
)Da
y 8
Day
14Da
y 21
Day
28
Day
10
Base
line
Day
0−Pr
eDa
y 0−
1hDa
y 0−
4hDa
y 1
Day
2Da
y 4
Day
7Da
y 7
(Rim
+1 h
)Da
y 7
(Rim
+4 h
)Da
y 8
Day
14Da
y 21
Day
28
Day
10
Base
line
Day
0−Pr
eDa
y 0−
1hDa
y 0−
4hDa
y 1
Day
2Da
y 4
Day
7Da
y 7
(Rim
+1 h
)Da
y 7
(Rim
+4 h
)Da
y 8
Day
14Da
y 21
Day
28
Day
10
Base
line
Day
0−Pr
eDa
y 0−
1hDa
y 0−
4hDa
y 1
Day
2Da
y 4
Day
7Da
y 7
(Rim
+1 h
)Da
y 7
(Rim
+4 h
)Da
y 8
Day
14Da
y 21
Day
28
Day
10
Base
line
Day
0−Pr
eDa
y 0−
1hDa
y 0−
4hDa
y 1
Day
2Da
y 4
Day
7Da
y 7
(Rim
+1 h
)Da
y 7
(Rim
+4 h
)Da
y 8
Day
14Da
y 21
Day
28
Day
10
0.0
0.5
1.0
1.5
2.0
−0.5
0.0
0.5
1.0
1.5
0.0
0.5
1.0
1.5
0.0
0.5
1.0
−0.5
0.0
0.5
−0.5
0.0
0.5
0.0
0.5
1.0
1.5
2.0
−0.5
0.5
1.5
2.5
−0.6
−0.2
0.2
0.6
0.0
0.4
0.8
1.2
0.0
0.5
1.0
1.5
0.0
0.2
0.4
0.6
0.0
0.5
1.0
1.5
0.0
0.5
1.0
−0.4
0.0
0.4
−0.2
0.0
0.2
0.4
−1.0
−0.5
0.0
Prostate Stem Cell An�gen (PSCA) is a cell surface protein overexpressed in approximately 50-80% of pancrea�c cancers.1-3 BPX-601 is an autologous GoCAR-T cell therapy engineered to express a PSCA-CD3ζ CAR and the inducible MyD88/CD40 (iMC) coac�va�on domain. Ac�vated by the ligand rimiducid (Rim), iMC is designed to boost CAR-T performance in solid tumors. The safety and ac�vity of BPX-601 ac�vated with Rim in PSCA+ metasta�c pancrea�c cancer is currently being assessed in a Phase 1/2 clinical trial, BP-012 (NCT02744287).Phase 1 of BP-012 is a 3+3 dose escala�on of BPX-601 (1.25-5 x 106 cells/kg) administered on Day 0 with a single, fixed-dose of Rim (0.4 mg/kg) on Day 7 in subjects with previously treated PSCA+ metasta�c pancrea�c cancer. A total of 18 subjects have been enrolled and treated with BPX-601. Fourteen subjects received rimiducid on Day 7 following cell infusion. Cohorts 0 (n=3), 3 (n=3), 4 (n=3) and 5A (n=4) received single dose of Cy lymphodeple�on (LD). Cohort 5B (n=5) subjects re-ceived Flu/Cy LD over 3 days followed by BPX-601 (5 x 106 cells/kg) and Rim (0.4 mg/kg) on Day 7. The current study presents a brief biomarker summary analysis from all cohorts (n=18) of BPX-601 cell prolifera�on and persistence as well as the produc�on of several CAR-T-associated cytokines (IFN-γ, IL-6, IP-10, and GM-CSF). An in-depth biomarker analysis of Cohort 5B (n=5) was per-formed, including serum cytokine profiles (n=5), tumor infiltra�on by GoCAR-T cells and differen-�al gene expression from available tumor biopsies collected (n=3).
Stalk
Linker
VH VL
Rimiducid
QStalk
Linker
VH VL
Rimiducid
Q
BP-012 STUDY DESIGN
PATIENTS
BIOMARKER SAMPLING TIMELINE
Table 1. BP-012 Pa�ent Demographics and Clinical Characteris�cs
Cohort 0: Lead-in safety cohort with cells only and no rimiducidCohorts 3-5B: Increasing cell doses based on a 3+3 dose escala�on design followed by fixed dose of rimiducid on Day 7Cohort 5C: Maximum cell dose (5 x 106 cells/kg) followed by rimiducid on Day 7 and every 7 days therea�er un�l unacceptable toxicity or progression of disease.
Cy, cyclophosphasmide; Flu, fludaradine; PSCA, prostate stem cell an�gen; RDE, recommended dose for expansion
Current Status of Phase 1: enrollment ongoing in Cohort 5C (mul�-dose rimiducid)
Cohort 5B:5 x 106 cells/kg
PSCA+ advanced pancrea�c
cancer
Cohort 0:1.25 x 106 cells/kg
Cohort 3:1.25 x 106 cells/kg
Cohort 5C:5 x 106 cells/kg
Cohort 5A:5 x 106 cells/kg
Cohorts 3, 4, 5:
Single-doserimiducid0.4 mg/kgCohort 4:
2.5 x 106 cells/kgCohort 4:
2.5 x 106 cells/kg
Phase 2
Rou�ne safety and efficacy evalua�ons
up to 60 monthsDay 0 Day 7
Cohorts 0, 3, 4, 5ALymphodeple�on
(Cy)Apheresis
Cohort 5C:Mul�-dose rimiducid
0.4 mg/kgCohorts 5B, 5C
Lymphodeple�on(Flu+Cy)
Every 7Days
Cy: Day -3Flu/Cy: Days -5, -4, -3
RDE
Phase 1
Tumor Infiltra�on and Cytokine Biomarkers of Prostate Stem Cell An�gen (PSCA)-Directed GoCAR-T® Cells in Pa�ents with Advanced Pancrea�c TumorsJoanne Shaw,1 Brandon Ballard,1 Xiaohui Yi,1 Aditya Malankar,1 Ma�hew R. Collinson-Pautz,1 Kwame Okrah,1 Carlos R. Becerra,2 Paul Woodard,1 Aaron E. Foster11Bellicum Pharmaceuticals, Inc., Houston, TX; 2Baylor University Medical Center, Dallas, TX. Corresponding Author: [email protected]
GoCAR-T CELLS INFILTRATED TUMOR METASTASES
• BPX-601 GoCAR-T cells exhibited enhanced survival and persistence up to 9 months.• Ac�va�on of BPX-601 GoCAR-T cells mediated upregula�on of immunomodulatory cytokines in pa�ents.• BPX-601 GoCAR-T cells infiltrated metasta�c pancrea�c tumors.• Changes in tumor microenvironment gene expression consistent with a produc�ve CAR-T cell immune response were observed in pa�ents treated with BPX-601 GoCAR-T cells ac� vated with rimiducid.• Pa�ents are currently being enrolled in BP-012 study Cohort 5C to assess the safety and efficacy of repeated BPX-601 ac�va�on with weekly rimiducid administra�on.
CONCLUSIONS
Figure 7. Differen�al gene expression in response to treatment with BPX-601 and rimiducid were evaluated in available biopsies from cohort 5B pa�ents (n=3) using the Nanostring PanCancer IO 360 panel. (A) The log fold change in gene expression between the baseline and on-treatment samples was evaluated and consistent changes were observed in all pa�ents (n=3, p < 10%). Genes highlighted in red are poten�ally associated with CAR-T ac�vity. (B) The rela�ve contribu�on from genes in defined func�onal categories to differen�al gene expression observed in all 3 pa�ents. Upregulated genes were most associated with immune cell localiza�on to tumors, while downregulated genes were most associated with myeloid cell ac�vity. (C) Individual gene expression profiles for each pa�ent evaluated (n=3). Upregula�on of interfer-on-responsive genes was observed in pa�ent 5B-5, together with genes associated with effector T cell func�on and downregula�on of PSCA which is indica�ve of a produc�ve, effector T cell response. Pa�ent 5B-5 also had the highest levels of tumor infiltra�ng BPX-601 cells (Figure 6B-C). (D) Func�onal annota�on of individual pa�ent gene expression profiles revealed a diverse pa�ern of func�onal a�ributes.
A B
C
TLR5
MFG
E8IL
16P4
HA1
HEY1
CXCR
3BN
IP3
MAG
EA1
IL6R
TNFS
F9U
BA7
TNFR
SF9
LILR
A3CD
247
TSLP
IFI3
5CD
7TN
FRSF
18M
AGEA
4ST
AT1
BLK
TWIS
T2SI
GLEC
1IL
21R
PLA1
AGZ
MB
CASP
1IL
10BP
X-60
1HS
D11B
1TD
O2
HLA−
DRB5
−2−1
01
23
4
Cohort 5B Differen�ally Expressed Genes (n=3)
Log2
FC(P
re/P
ost) Downregulated Genes
2 2. 2%
3 3. 3%1 1. 1%
1 1. 1%
2 2. 2%
Upregulated Genes
2 3. 1%
1 8. 5%
1 2. 3%1 2. 3%
1 0. 8%
7 .7%
7 .7%
7 .7%
D
Immune Cell Localization to TumorsT Cell Priming and ActivationKilling of Cancer CellsMyeloid Cell ActivityCommon Signaling Pathways
Pa�ent 5B-2
4 1. 7%
8 .3%8 .3%
1 6. 7%
2 5%
Pa�ent 5B-2
2 0. 0%
2 0. 0%1 3. 3%
1 0. 0%
1 0. 0%
1 3. 3%
1 0. 0%
Pa�ent 5B-5
3 3. 3%
1 6. 7%
1 6. 7%
2 5%
8 .3%
Pa�ent 5B-5
1 8%
1 2. 8%
2 0. 5%1 8%
1 2. 8%
1 2. 8%
Immune Cell Localization to TumorsT Cell Priming and ActivationKilling of Cancer CellsMyeloid Cell ActivityCancer Antigen PresentationRecognition of Cancer Cells by T CellsStromal FactorsTumor-Intrinsic Factors
Pa�ent 5B-4
2 2. 2%
2 2. 2%
1 1. 1%2 7. 8%
1 6. 7%
Pa�ent 5B-4
2 3. 3%
1 0. 0%
1 0. 0%2 6. 7%
1 0. 0%
1 0. 0%
6 .7%
Upregulated Genes
Downregulated Genes
CD3+ T Cell LevelsA C D
Figure 6. Biopsies taken at baseline and on-treatment (Day 14-21) from lymph node (5B-2), liver (5B-4) and omentum (5B-5) were stained for CD3 (IHC), BPX-601/CAR (RNAScope ISH), and PSCA (RNAScope ISH). (A) Percent CD3+ lymphocytes in tumor stayed rela�vely the same between baseline and on-treatment. (B) Infiltra�on of CAR+ cells into tumor �ssue was observed in all on-treatment specimens (n=3). (B) CAR+ cells were located both in the tumor and the stroma in all pa�ents (n=3). (C) The highest intensity of CAR staining was observed in pa�ent 5B-5, who also had the highest number of infiltra�ng CAR+ cells. (D) CAR+ cells were observed proximal to tumor, representa�ve images; CD3 (blue) and CAR (red). (E) PSCA expression was observed in baseline and on-treatment specimens, representa�ve images showing PSCA (red).
E
CAR+ Cell Infiltra�on Total Infiltra�ng CAR+ Cells
Baseline On Treatment(D14-D21)
0
20
40
60
80
100
% C
D3+ o
f Tot
al C
ells
% C
AR+ o
f Tot
al C
ells
Baseline On Treatment(D14-D21)
0
1
2
3
4
5
TumorStroma
CAR Expression Intensity
CAR(BPX-601) = redCD3 = blue
B
COHORTS 0-5B BIOMARKER OVERVIEW
GoCAR-T ACTIVATION INCREASED IMMUNOMODULATORY CYTOKINES
COHORT 5B BIOMARKER RESULTS
Figure 3. (A) Persistence of BPX-601 cells in cohort 5B pa�ents was evaluated by vector copy number (VCN) analysis. BPX-601 cells expanded in all pa�ents (n=5) and persisted up to 9 months 9. Four of 5 (80%) pa�ents has measure BPX-601 VCN at last �me point available. (B) Rapid reduc-�on and rebound in BPX-601 VCN was observed in all pa�ents (n=5) following rimiducid infusion.
0 140
50
100
150
200
0
2000
4000
6000
8000
100005B-3
Days Post-BPX-601
Cells
/mcl BPX-601
(copies/µgD
NA)
Rim
7
CD3+CD4+CD8+
VCN (right axis)
Tocilizumab (CRS)
Dexamethasone (Encephalopathy)
A
0 140
50
100
150
200
250
0
20000
40000
600005B-1
Days Post-BPX-601
Cells
/mcl BPX-601
(copies/µgD
NA)
Rim
7
0 140
50
100
150
200
0
5000
10000
150005B-4
Days Post-BPX-601
Cells
/mcl BPX-601
(copies/µgD
NA)
Rim
7
A
PROLIFERATION & PERSISTENCE ACTIVATED T CELL REDISTRIBUTION
Figure 4. (A) A rapid, transient reduc�on and rebound in the absolute number of total T cells (CD3) and CD4+ and CD8+ T cell subsets in cohort 5B pa�ents (n=5) was observed following rimiducid in-fusion, concurrent with the decrease in BPX-601 VCN. This suggests redistribu�on of ac�vated T cells from the blood stream poten�ally by vascular adhesion associated with T cell transmigra�on.
Rela�onship between Serum Cytokines and BPX-601 VCNCohort 5B (n=5)
A
Figure 5. Serum cytokine levels in Cohort 5B pa�ents (n=5) were evaluated at serial �mepoints using a mul�plex assay. (A) Analytes were grouped by immune func�on (Th1 proinflammatory, Th2 proinflammatory, Chemotrac�ve, Th17 proinflammatory, and Regulatory) and the sum of mean cytokine levels at each �mepoint was plo�ed in the stacked bars. The do�ed line represents the mean VCN for Cohort 5B (n=5). Serum cytokine levels increased at Day 4 following BPX-601 infusion and within 24 hours of rimiducid infusion, with peak cytokine levels observed concurrently with increasing VCN. This data supports rimiducid-mediated T cell ac�va�on. (B) Serum concentra�on of individual analytes normalized to baseline was plo�ed, with mean levels from all Cohort 5B pa�ents (n=5) shown in pink. Day 7 (pre-rimiducid) indicated by enlarged Yellow data points. Data from individual pa�ents are plo�ed (gray lines) along with the median and interquar�le ranges (boxes).
B
Cohort 0 1.25x106
(Cy)
Cohort 3 1.25x106
+ Rim (Cy)
Cohort 4 2.5x106
+ Rim (Cy)
Cohort 5A 5x106
+ Rim (Cy)
Cohort 5B 5x106
+ Rim (Flu/Cy)
101
102
103
104
105
BPX-
601
Peak
VCN
0 1 105 2 105 3 105 4 105
Cohort 0 1.25x106(Cy)
Cohort 3 1.25x106+ Rim (Cy)
Cohort 4 2.5x106+ Rim (Cy)
Cohort 5A 5x106+ Rim (Cy)
Cohort 5B 5x106+ Rim (Flu/Cy)
BPX-601 VCN AUC(copies/ g * day)
D0-D7
D7-D∞
BPX-601 VCN AUC
Figure 2. BPX-601 vector copy number (VCN) was quan�tated by qPCR from isolated PBMC samples. (A) Area under the curve (AUC) for BPX-601 VCN over �me was calculated by the linear trapezoidal method using PK Solver. Pa�ents without an evaluable terminal elimnia�on phase were omi�ed from the D7-Dinfinity dataset. (B) Peak BPX-601 VCN observed. (C) Serum cytokines were measured in pa�ent samples using a mul�plex Luminex assay. Each box shows weighted-mean fold-change serum concenta�on (pg/ml) from baseline for CAR-T-associated cytokines, pooling IFN-γ, IP-10, GM-CSF, and IL-6 together.
Peak BPX-601 VCNA B C Pooled Cytokine Profiles (IFN-γ + IP-10 + GM-CSF + IL-6)
GoCAR-T PLATFORM
BPX-601 GoCAR-T DESIGN
TARGET ANTIGEN: PSCA
•Small, GPI-anchored cell-surface protein of the Thy-1/Ly-6 family
•Expression observed in 50-80% of pancrea�c ductal adenocarcinomas1-3
•Low basal expression on normal prostate epithelium, urinary bladder, kidney, esophagus, stomach, and placenta3
•Low toxicity profile with PSCA-targeted an�bodies in prostate and pancrea�c cancer7,8
Figure 1. PSCA expression measured by qPCR in BP-012 pancrea�c tumor screening samples. Data as of October 15, 2019
PSCA-Targeted 1st Genera�on CAR+iMC-ac�vated GoCAR-T Cells:
Increase persistence, survival, and func�on of adop�vely transferred CAR-T cells4,5
S�mulate endogenous immunity (adjuvant effects): •Produc�on of immunomodulatory cytokines4,5
•Upregula�on of cos�mulatory molecules6
FKBP scFv CD3ζCD8αMyD88 CD40 2A QFKBPψ
INDUCIBLE COSTIMULATION 1st GENERATION CAR
LTR LTR
PSCA-CAR.CD3ζ
MyD88/CD40 Coac�va�on Domain
CD3ζ
Stalk
Linker
VH VL
Rimiducid
FKBP
CD40
MyD88
Q
FKBP
BACKGROUND
ProinflammatoryN-
F
Th1 IF
G-CSGM-CSF
Proinflammatory-5-7
Th2 ILIL
e0
-81
1
Chemotrac�vIP-1ILMCP-MIP-
-67A
-1
Th17 ProinflammatoryILIL-1IL
y
-10RA
RegulatorVEGFILIL-1
(right axis)BPX-601
TNF-αIL-2
Immune Cell Localiza�on to TumorsMyeloid Cell Ac�vityT Cell Priming and Ac�va�onKilling of Cancer CellsRecogni�on of Cancer Cells by T CellsRelease of Cancer Cell An�gensCancer An�gen Presenta�onTumor-Intrinsic FactorsStromal Factors
Upregulated (Top 10)
Downregulated (Bo�om 10)Effector T Cell Func�on
BPX-601 IV:5 x 106 cells/kg
PSCA+ advanced
PancCa
Rimiducid IV:0.4 mg/kg
D0(pre, 1hr, 4hr)
D7(pre, 1hr, 4hr)
Apheresis
Lymphodeple�on(Flu+Cy)
Days-5, -4, -3
Baseline(-14 to -1)
D2 D42D8x3
D4x3
D28 D35D21D17D14D10 x1/Mo.M2-6
M9, M12
EOT
x1
On-Treatment
= biopsy (IHC/ISH, Nanostring gene expression); added to BP-012 protocol star�ng for Cohort 5B
= blood (whole blood: VCN qPCR; serum: cytokine mul�plex, baseline-D42 only)
D1
BP-012 Cohort 5B Schedule Shown
F
BaselineOn-Treatment
(D14-21)
Tumor PSCA Expression (ISH)
PSCA = red
5B-2
5B-5
5B-4
BBPX-601 VCN Day 0 - 270 (M9) BPX-601 VCN Day 0 - 14 Absolute T Cell Counts and BPX-601 VCN Day 0 -14
BP-012101
102
102
103
104
105
106
107
PSCA ExpressionPancrea�c Tumors
(54.8% Posi�ve, n = 40/73)
BLQLOQ
CutoffPSCA
Cop
ies /
1e6
copi
es h
ACTB
le� axis
Pa�ent 5B-2 (Lymph node) Pa�ent 5B-5 (Omentum)Pa�ent 5B-4 (Liver)
TumorStroma
Pa�ent 5B-2
Pa�ent 5B-4
Pa�ent 5B-5
CD8A
PDL1
EOMES
GZMA
GZMB
PRF1
0
2
Effector T CellFunc�on Genes
4
Log2FC(Pre/Post)
Day
0-P
re
Day
0-1
h
Day
0-4
h
Day
1
Day
2
Day
4
Day
7
Day
7 (R
im+1
h)
Day
7 (R
im+4
h)
Day
8
Day
10
Day
14
Day
21
Day
280
50
100
150
200
102
103
104
105
Conc
. / B
asel
ine
(pg/
ml) BPX-601 copies/μg DN
A
5B-2 5B-4 5B-5
Adj. Normal
TumorStroma
Tota
l CAR
+ Cel
ls
0
100
200
300
400
500
77
82 119
161
38
19
212
238
5A-1
5B-1
0-10-20-3
3-13-23-3
4-1
4-34-2
5A-25A-35A-4
5B-25B-3
5B-55B-4
BaselineDay 0−PreDay 0−1hDay 0−4hDay 1Day 2Day 4Day 7Day 7 (Rim+1h)Day 7 (Rim+4h)Day 8
Day 14Day 21Day 28
Cohort0 3 4 5A 5B
0
5
10
Fold-Change(Baseline)
Day 10
Days Post-BPX-601
BPX-
601
(Cop
ies/µg
gDN
A)
0 10 20 30 40 50 60101
102
103
104
105
90 180 270LOQ
Rim
Days Post-BPX-601
BPX-
601
(Cop
ies/µg
gDN
A)
0 14101
102
103
104
105
LOQ
5B-1*
5B-25B-35B-45B-5^
Rim
7
0
2
4
65B-2
5B-55B-4
H-Sc
ore
(BPX
-601
)
Tumor Stroma
Cohort LD Regimena
BPX-601 Dose
(106 cells/kg)
Rim(Y/N) Age/Sex
# Prior Systemic
Therapiesb
Prior
Immunotherpy
History of Surgical PSCA
(copies)Best
Responsed
0 Cy 1.25N 0-1 50/F 1 N N 5,071 N/Ee
N 0-2 58/F 3 N Y 377,444 N/Ee
N 0-3 65/F 5 N N 15,494 N/Ee
3 Cy 1.25Y 3-1 59/F 2 DC vaccine
(WT1, mesothelin)
N 34,342 SD
Y 3-2 70/M 1 N N 7,367 SDY 3-3 58/F 1 N N 31,429 PD
4 Cy 2.5Y 4-1 71/F 2 N N 7,686 SDY 4-2 65/M 2 Anakinra Y 8,243 PDY 4-3 60/F 3 N N 354730 SD
5A Cy 5.0Y 5A-1 64/M 1 N N 19,533 N/Ae
Y 5A-2 61/M 2 Anakinra Y 14,238 PDN 5A-3 59/M 5 Pembro N 969,094 N/Ae
Y 5A-4 55/M 2 N N 52,797 SD
5B Flu/Cy 5.0
Y 5B-1 77/M 2 N Y 18,980 SDY 5B-2 56/M 4 N Y 201,277 PDY 5B-3 72/M 1 N N 21,099 SDY 5B-4 68/F 1 N N 54,877 PDY 5B-5 58/M 1 N N 149,110 SD
aCy dose = 1 g/m2 Day -3; Flu/Cy dose = Cy 500 mg/m2 + Flu 30 mg/m2 Days -5, -4, and -3bPrior lines of systemic therapy regardless of intentcHistory of pancreatoduodenectomydResponse Criteria as measured by RECIST 1.1; e
Pa�ent
Cohort 0 subjects not evaluable per RECIST 1.1; Subject 5A-1 NED at baseline; Subject 5A-3 off study prior to first scan due to AE associated with pro-gressive disease
Safety data for Cohorts 0-5B reported in Becerra et al., Annual Mee�ng 2019, American Society of Clinical Oncology
Cy, cyclophosphamide; Flu, fludarabine; N/A, not available; N/E, not evaluable; NED, no evidence of disease; Pembro, pembrolizumab; PD, progress-ive disease; PSCA, prostate stem cell an�gen; Rim, rimiducid; SD, stable disease.
An�-Cancer An�-CancerResec�onc
Inves�ga�onal
Table 2. Biomarker Sampling by Cohort
Rimiducid TCR Complexβα
CARCD3ζ
Prolifera�onPersistence
CAR-T Enhanced by iMC Co-ac�va�on
Ac�vatedImmune S�mula�on
&Cell Survival
Target-SpecificCytotoxicity
iMC
The GoCAR-T pla�orm incorporates the iMC coac�vator into CAR-T cells to provide powerful ac-�va�on of immune pathways, downstream of MyD88 (innate) and CD40 (adap�ve) signaling. Ac-�va�on of iMC with rimiducid promotes cell prolifera�on, persistence, secre�on of immuno-modulatory cytokines, and resistance to T cell exhaus�on4,5.
DIFFERENTIAL GENE EXPRESSION IN TUMOR MICROENVIRONMENT
*Pa�ent 5B-1 received cor�costeroids Day 8 for grade 2 encephalopathy. ^Pa�ent 5B-5 received tocilizumab Day 8 for grade 2 cytokine release syndrome
Cohort
Cohort 01.25 x 106 cells/kg
(Cy)
Cohort 31.25 x 106 cells/kg
+Rim(Cy)
Cohort 42.5 x 106 cells/kg
+Rim(Cy)
Cohort 5A5 x 106 cells/kg
+Rim(Cy)
Cohort 5B5 x 10
6 cells/kg
+Rim(Flu/Cy)
n=3 n=3 n=3 n=4 n=5BPX-601 Tracking(Vector Copy Number) √ √ √ √ √
Serum Cytokines √ √ √ √ √
Tumor Biopsy*(IHC, ISH, NanoString) NA NA NA NA √
(n=3/5)
# of Pa�ents
(Mul�plex)
*Baseline and on-treatment tumor biopsies added to BP-012 clinical protocoal star�ng for Cohort 5B
No Data
1. Argani P, et al. Cancer Res. 2001;61:4320–4324.2. Wente MN, et al. Pancreas. 2005;31:119–125.3. Abate-Daga D, et al. Hum Gene Ther. 2014;25(12):1003–1012.4. Mata M, et al. Cancer Discov 2017;7:1306-1319.5. Foster AE, et al. Mol Ther. 2017;25(9):2176–2188.6. Bellicum data on file.7. Morris MJ, et al. Ann Oncol. 2012;23:2714–2719.8. Wolpin BM, et al. Ann Oncol. 2013;24:1792–1801.
REFERENCES
The authors would like to acknowledge all pa�ents, their families, and caregivers for par�cipa�ng in this clinical trial, along with the inves�gators and their staff.
Presented at the American Society of Clinical Oncology Gastrointes�nal Cancers Symposium - January 23 - 25, 2020, San Francisco, CA
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NF-κB NFATc
IL-2