Corporate Presentation - August 2021 Listed on Tokyo Stock Exchange (Mothers) Code: 4594
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Corporate Presentation
August 2021
Listed on Tokyo Stock Exchange (Mothers)
Code: 4594
Disclaimer
The material that follows is a presentation of general background information about BrightPath Biotherapeutics Co., Ltd. (“BrightPath”) as of the date of this presentation.
This material prepared solely for information purpose and is not to be construed as a solicitation or an offer to buy or sell any securities and should not be treated as giving
investment advice to recipient.
This material and any material distributed in connection with this presentation may contains forward-looking statements, beliefs or opinions regarding BrightPath’s future
business, future position and result of operations, including estimates, forecasts, targets and plans for BrightPath. Without limitation, forward-looking statements often
include words such as “target”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “ensures”, “will”, “may”, “should”, “would”, “could”, “anticipate”,
“estimates”, “projects” or similar expressions or the negative thereof. Such forward-looking statements involve known and unknown risks, uncertainties and other factors
which may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by
such forward-looking statements. Such forward-looking statements are based on numerous assumptions regarding our present and future business strategies and the
environment in which BrightPath will operate in the future. The important factors that could cause our actual results, performance or achievements to differ materially from
those in the forward- looking statements include, among others, risks associated with product discovery and development, uncertainties related to the outcome of clinical
trials, slower than expected rates of patient recruitment, unforeseen safety issues resulting from the administration of our products in patients, uncertainties related to
product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and
markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with
affiliated entities, changes and developments in technology which may render our products obsolete, and other factors. These factors include, without limitation, those
discussed in our public reports filed with the Tokyo Stock Exchange and the Financial Services Agency of Japan. Although BrightPath believes that the expectations and
assumptions reflected in the forward-looking statements are reasonably based on information currently available to BrightPath's management, certain forward-looking
statements are based upon assumptions of future events which may not prove to be accurate.
BrightPath does not undertake to update any of the forward-looking statements contained in this presentation or any other forrard-looking statements it may make, except
as required by law or stack exchange rule.
No representation or warranty, either express or implied, by BrightPath is made as to the accuracy, fairness, or completeness of the information presented herein and no
reliance should be placed on the accuracy, fairness, or completeness of such information. Various factors may cause actual results to differ materially from those
described in this material.
The presentation contains information on drugs currently under development. Nothing contained herein should be considered any solicitation, promotion, advertisement, or
medical advice.
The information contained in this material may be changed without prior notice. In addition, BrightPath may alter, modify or otherwise change in any manner the contents
of this presentation, in its own discretion without the obligation to notify anu person of such revision or changes. Neither BrightPath nor its sources or informants assume
any responsibility or liability for any loss or damage that may be incurred by those who will rely on the information in this document.
This presentation and its contents are proprietary confidential information and may not be reproduced, published or otherwise disseminated in whole or in part without
BrightPath’s prior written consent. These materials are not intended for distribution to, or use by, any person or entity in any jurisdiction or country where such distribution
or use would be contrary to local law or regulation.
In the event of any inconsistency between the statement in the English-language presentation and the statement in the Japanese-language presentation, the statements in
the Japanese-language version should prevail.
1
Pipeline of BrightPath
Development Focus
Cancer immunotherapeutics as a main growth driver of
pharmaceuticals
Cancer Immunotherapeutics
($94.7bn)
CAGR 20.2%
source : EvaluatePharma, July 2020
3
Approved Cancer Immunotherapeutics
Increasing numbers of immunotherapeutics have been approved globally,
with the revenues of the marketed products forecast to reach $50bn (2024e)
Enhancement Immunity Cycle and
of activation Approved Immunotherapeutics ( ) : estimated sales for 2024, EvaluatePharma January 2020
Anti-CTLA-4 antibody
Yervoy ($2.0bn)
4 Delivery of cancer-
Blood vessel
specific cells
5
Anti-PD-1 antibody
T cell
CAR-T
Keytruda ($23.3bn) Kymriah ($1.0bn),
Opdivo ($10.5bn) Yescarta ($2.0bn)
Jemperli (new) Breyanzi(new)
3
Anti-PD-L1 antibody 6 Abecma (new)
Tecentriq ($5.3bn ) T cell (2017-)
Imfinzi ($2.2bn) Cancer
Bavencio (new) antigen
(2011-) Cancer cell
Removal of inhibitory
Induction of 2 Dendritic cell signals
Cancer antigen
antigen Anti-PD-1 antibody
recognition 7 Keytruda ($23.3bn)
Dendritic cell Immune Opdivo ($10.5bn)
checkpoint
Jemperli (new)
vaccine
Provenge (-) 1 Dead cancer cell Anti-PD-L1 antibody
(2009) Tecentriq ($5.3bn )
Imfinzi ($2.2bn)
Bavencio (new)
Promotion of (2014-)
antigen release Adapted from Chen & Mellman, Immunity 2013
Oncolytic virus
T-VEC (-) (2015) 4
BrightPath Pipeline
Focused on cancer immunotherapies
Multiple modalities (vaccine, antibody, cell therapy) Clinical Stage
4
Adoptive cell transfer
T cell 5
iPS-NKT (Investigator-initiated)
BP2301 (HER2 CAR-T)
3
Enhancement 6
of antigen- T cell
presentation Cancer
antigen
BP1401 Cancer cell
TLR9 agonist
2 Dendritic cell
Cancer antigen
Induction of antigen 7 Blockade of inhibitory
recognition Immune signals
checkpoint
GRN-1201 BP1200 (CD73)
Four tumor associated Ag 1 Dead cancer cell BP1210 (TIM-3)
BP1101 BP1202 (not disclosed)
Personalized NeoAg
Promotion of antigen BP1211 (PVR)
BP1209
Next generation-NeoAg
release
BP1206 (HLA-DR)
Adapted from Chen & Mellman, Immunity 2013
5
Pipeline
6
Near-term Events
FY2020 FY2021 FY2022
Cancer vaccines
GRN-1201 Tumor associated antigens P2 Stage 1
Read-out
BP1101 Neoantigen FY2021 4Q
ESMO 2021
BP1209 Neoantigen+Delivery 1005P ”A new platform of personalized
neoantigen cancer vaccines directed by
BP1401 TLR9 agonist checkpoint inhibitor antibodies to
improve cancer immunity.”
Cells
iPS-NKT iPS cell-derived iNKT cells IND
IND
BP2301 HER2 CAR-T FY2022 1Q
Antibodies
ESMO 2021
BP1200 CD73 987P “A novel therapeutic antibody
BP1210 TIM-3 against CD73 that ameliorates the
tumor microenvironment and improves
BP1202 (not disclosed) the efficacy of cancer immunotherapy”
BP1206 HLA-DR
BP1209 PVR
7
GRN-1201
Cancer vaccine comprised of four TAAs induces cytotoxic T cell to
eradicate cancer cells
Combination with immune checkpoint blockade antibodies increases
antitumor effects
4
T cell 5
3
6
T cell
Cancer
antigen Antigen = Marker of Cancer Vaccine- Vaccine-
Cancer cell Cancer cell induced Cancer cell induced
T cell Immune checkpoint T cell
molecules bind and
send a suppressive
signal to T cells
2 Dendritic cell Eliminate cancer cells
Cancer antigen expressing antigens
identical to vaccines
7
Immune
checkpoint
1 Dead cancer cell
Cancer cell Killing T cell
Induction of antigen
recognition
GRN-1201
Four TAAs Anti-PD-1 mAb
8
GRN-1201 (cont’d)
Address unmet medical needs in NSCLC
First-line therapy
PD-L1 expression ≧50％
GRN-1201 added to first-line pembrolizumab
therapy to increase responders
Anti-PD-1
PD-L1 expression 22% Not effective in 55%
≧50％ or not
est. # of pts: 71,000 (US+ EU+ JP, 2025) ＊
52% PD-L1 expression 1-49％
30% Anti-PD-1
+
Chemotherapy
PD-L1 expression
≧1％ or not Not effective in 45%
First-line therapy Second-line therapy
PD-L1 expression < 1％
48%
Chemotherapy Anti-PD-1
Not effective
40% not in 80%
eligible
＊ Source: Datamonitor Healthcare® | Informa, 2020, Dietel et al. Lung Cancer 134(2019), BrightPath Biotherapeutics
9GRN-1201 (cont’d)
Ongoing Phase 2 trial of GRN-1201 in addition to pembrolizumab as first-
line NSCLC therapy
A Pilot, Open-Label, Multi-Center, Multi-Dose Study of GRN-1201 Added to
Study title Pembrolizumab in Subjects with Non-Small Cell Lung Cancer with High PD-L1
Expression
US clinical trial no. NCT03417882
Investigational
GRN-1201: Four HLA-A2＊1-restricted peptides
product
PD-L1 positive non-small-cell lung cancer
Target
PD-L1 positive (TPS＊2 ≥ 50%)
Primary endpoint Objective Response Rate
Concomitant drug Pembrolizumab (Keytruda)
64
Sample size
Simon's Two-Stage Design
Method Open-label, multi-center
＊1 This 55% group consists of 50% of the American or European subjects and 40% of the Japanese subjects.
＊2 TPS: Tumor Proportion Score (percentage of cells expressing PD-L1 on their surface among all tumor cells)
10GRN-1201 (cont’d)
Preliminary analysis in the initial stage of Phase 2 supports the mechanistic
hypothesis of GRN-1201, suggesting that the immune response may
contribute to better clinical outcome 180
ELISPOT (IFNγ production
症例A cell count) - Case A
Spot numbers/10 PBMC count
Peptide A
160 Peptide B
140 Pepride C
Change in tumor target lesions (as of May 2020) 120 Peptide D
100
PR SD (best target legion response)
6
80
30 60
40
20 20
Change in tumor target lesion (%)
0
10 0 19 43 (Weeks)
ELISPOT (IFNγ production
症例B cell count) - Case B
0
Spot numbers/10 PBMC count
180
160 Peptide A
Peptide B
-10 140 Pepride C
120 Peptide D
6
-20 100
* 80
60
-30 40
20
n.a.
-40 0
0 19 43 (Weeks)
-50
ELISPOT (IFNγ production
症例C cell count) - Case C
Spot numbers/10 PBMC count
180
-60 160
Peptide A
Peptide B
140 Pepride C
-70 120 Peptide D
100
0 10 20 30 40 50 60
6
80
Weeks after the initial administration 60
40
20
* Assessed PD after the observation point due to the development of new lesions 0
0 19 43 (Weeks)
By Direct ELISPOT (24h)
11iPS-NKT
Novel allogeneic cell therapy using iPS cell-derived invariant NKT cells
iNKT cells, unique subset of T cells, are implicated in the regulation of broad immune responses, but their limited
frequency had been an obstacle to acquire sufficient numbers of iNKT cells from patients to induce effective
antitumor immune responses of iNKT cell-based immunotherapy
iPSC technology made it possible to reprogram human iNKT cells to pluripotency and subsequently re-
differentiate into functional iNKT cells demonstrating anti-tumor efficacy
The iPSC-derived iNKT cells are functionally recovered and available in an unlimited supply from iPSCs
Adoptive cellular
transfer Indirect
iPS-NKT Indirect
killing
Cancer cell
(Phase 1) killing
NK cell
killing
Direct
NK receptor
T cell
Cancer
antigen
Cancer cell T cell Dendritic cell NKT cell
Lipid antigen
Regulate pro-
Activation Maturation
tumor Mφ
Dendritic cell
Cancer antigen
Immune
iNKT cells regulate broad
checkpoint antitumor immune responses
Macrophage
Dead cancer cell
12iPS-NKT (cont’d)
A first-in-human investigator-initiated trial in patient with head and neck
cancers started in June 2020
A Phase I study of iPS-NKT cell intra-arterial infusion therapy in patients with recurrent or
Study Title
advanced head and neck cancer (First in human study)
Recurrent or advanced head and neck squamous cell carcinoma, refractory or intolerant to
Subjects
standard treatment
To exploratory evaluate safety, efficacy and tolerability of intra-tumor nutrient artery administration
Purpose of iPS-NKT cells in patients with recurrent or advanced head and neck cancer after standard
therapy, which is difficult to treat radically.
Primary outcome Incidence of dose-limiting toxicity (DLT) at each dose
Secondary efficacy endpoints Response rate (RECIST ver.1.1)
Disease control rate (RECIST ver.1.1)
Secondary
outcome Secondary safety endpoints Occurrence of adverse events (type, frequency, severity, etc.)
Changes in clinical laboratory values
・Peripheral blood concentration transition of iPS-NKT cell
Exploratory ・Immune cell fraction
outcomes ・Blood cytokine concentration
Sample size 4-18
Study design Single site, open label, asymmetric, dose titration
Trial site Chiba University Hospital
Source： Chiba University
Originated and developed by RIKEN and BrightPath has an option to obtain an exclusive license to
develop, manufacture and sell and started collaborative research with RIKEN in April 2018
13iPS-NKT (cont’d)
Enhanced functionality of iNKT Cells
iPS cell-derived NKT cells promote secretion of anti-tumor IFN-γ and reduce
immunosuppressive IL-4
NKT line: iNKT cells before reprogramming into iPSC
iPS-NKT: iNKT cells re-diffrentiated from iNKT cell-
derived iPSC
DC: co-culture with dendritic cells
DC + Gal: co-culture with dendritic cells and antigens
DC DC NKT DC DC NKT DC DC NKT DC DC NKT (α-GarCer)
+ only + only + only + only NKT Only: without dendritic cells and antigens
Gar Gar Gar Gar
Increased In vitro cytotoxicity vs. iNKT cells before reprogramming into iPSC
Leukemia Non-small-cell lung Non-small-cell lung Colon cancer Colon cancer Pharyngeal cancer
cancer cancer
Killing activity (%)
Killing activity (%)
Yamada et al., Stem Cells. 2016
14iPS-NKT (cont’d)
In vivo Anti-tumor Activity
iPS-NKT cells suppress the proliferation of cancer cells
Tumor size (Fluorescence Intensity:
Total Flux [photons/second])
Source: Yamada et al., Stem Cells. 2016
15iPS-NKT (cont’d)
Established iPS master cell bank as renewable starting cell source
and robust cGMP process from iPSC to NKT cells to mass produce
homogeneous NKT cells
Pre-diagnosis Post-diagnosis
Autologous cell therapy
Patient Apheresis Production Administration
of single dose
Diagnosis
Allogeneic cell therapy 100+dosage
Healthy donor T cell Production
Master cell bank Substantial reduction of
allogeneic cell 10,000+dosage turnaround time from diagnosis
therapy
to administration
Healthy donor T cell Reprogramming Master cell Production Administration of
bank multiple doses
Reprogramming Process
iPSC iPS cell-derived
expansion NKT cell
NKT cell-derived iPS cell iPS single-cell clone Master cell
bank
Reprogramming
Re-differentiation
& Multiplication
into iPS cells
NKT cell
Cryopreserved stock
(for immediate use)
16iPS-NKT (cont’d)
Benchmarking CAR-transfected iPSC-derived effector-cell products for
expansion strategy
(IND filing year) Hematology CAR Solid tumor CAR
Un-
Company CD19 BCMA CD38 EGFR GPC3 MICA
modified
Fate Tx 2018 2020 2021 2022
iPSNK
Century Tx 2021 2022
Cytovia Tx 2021 2022 2022 2022
iPSNKT
BrightPath 2020
(RIKEN)
17BP2301
Autologous HER2 CAR-T cell therapy for solid tumors
HER2 is a clinically validated target and HER2 CAR-T has third party’s precedent
successful clinical outcome in sarcoma*
BP2301 demonstrates a stem cell memory-rich phenotype, which is expected to
improve the anti-tumor efficacy
Flow of CAR-T cell therapy
Adoptive cell transfer
HER2 CAR-T CAR gene transfer
(piggyBac)
CAR-T cell
T cell Multiplication
Kill cancer cells
CAR-T cell
Cancer cells Antigen
Signal transduction
Antigen binding site domain
Cancer antigen CAR-T cells
Cancer cell
T cell
Blood Drawing Administration
* HEROS2 study of HER2 CAR-T in patients with sarcoma conducted by Baylor College of Medicine showed one complete response and a response rate
of 18% (AACR2019) although most clinical studies of CAR-T for solid tumors have not been able to demonstrate CR.
18BP2301 (cont’d)
piggyBac transposon-based CAR gene transfer enables CAR-T cells
to maintain stem cell memory-like phenotype with self-renewing,
long-term persisting ability and durable antitumor effects
T cell differentiation and phenotypes Persistence of memory-rich CAR-T cells
Cell death
Self-renewal
Long-term persistence
Effector function
SCM: ステム・セル・メモリー
CM: セントラル・メモリー
SCM: Stem Cell Memory
EM: エフェクター・メモリー
CM: Central Memory
EFF: エフェクター
EM: Effector Memory
EFF: Effector
Memory-rich CAR-T Effector-rich CAR-T
19BP2301 (cont’d)
BP2301 cells exhibits dominant of stem cell memory phenotype
without early T cell exhaustion
TEFF TSCM PD-1
72.5 % 0.3 %
CD45RA
PD-1
TEM TCM
CCR7 CD3
SCM: Stem Cell Memory
CM: Central Memory
EM: Effector Memory
EFF: Effector
Source: Shinshu University, BrightPath
20BP2301 (cont’d)
Memory-rich BP2301 exhibits long-term functional persistence and
exhaustion resistance
BP2301 exhibits robust serial killing Tumor: Osteosarcoma cells(U2-OS)
E:T =1:1
Tumor alone
Round 1
+HER2 CAR-T cells
Tumor alone
Round 2
+HER2 CAR-T cells
Tumor alone
Round 3
+HER2 CAR-T cells
Source: Shinshu University, BrightPath
21BP2301 (cont’d)
BP2301 mediates robust antitumor function in vivo
Vehicle CD19.CAR HER2.CAR
Vehicle
Tumor size (Fluorescence Intensity: Total Flux
Day 6
Day14
[photons/second])
Day21 CD19.CAR
Day28
Day35
HER2.CAR
Day42
Source: Shinshu University, BrightPath Number of days from cancer cell transplant
22BP2301 (cont’d)
BP2301 demonstrates long-term functional persistence in vivo
BP2301 sustains antitumor function in re-challenge tumor mouse model
1 x 107
Re-challenge tumor
Primary tumor
Vehicle CD19.CAR HER2.CAR
Rechallenge
Day0
Rechallenge
Day7
Rechallenge
Day14
Source: Shinshu University, BrightPath
23BP1101
A fully-personalized neoantigen vaccine, induces immunity
against antigens derived from cancer-specific genetic mutations
(neoantigens), which are completely unique to every patient
T cell migration
Blood vessel
T cell
T cells infiltrate
cancer tissue
Lymph node
T cells recognize cancer
antigens presented on
the dendritic cells and
induce multiplication and T cells recognize cancer
activation antigens on the cancer cell
T cell surface
Cancer
antigen
Cancer cell
Cancer
Cancer antigens phagocytized by Dendritic cell
dendritic cells appear on the cell
surface
T cells kill cancer Immune
Kill cancer cells, release cells checkpoint
50 Cutaneous cancer antigens
squamous-cell
Dead cancer cell
Merkel-cell
Non-colorectal
40 (MMRd)
Melanoma
Objective Response Rate (%)
Colorectal
(MMRd)
30
Anal
Tumor mutation burden (neoantigen burden)
Renal-cell
Cervical
20 Hepatocellular Urothelial
Mesothelioma
NSCLC(squamous)
NSCLC(non-squamous)
Head and neck
correlates with the clinical response to anti-
checkpoint therapy, suggesting that neoantigens
Response rate
Endometrial Small-cell lung
Sarcoma Ovarian
10 Esophagogastric
Glioblastoma
Prostate
Uveal Adrenocortical Breast
Pancreatic Germ-cell Colorectal (MMRp)
are cancer immunity targets
0
1 10 20 30 40 50
Median No. of Coding Somatic Mutations per MB
Cancer somatic mutation burden (neoantigen burden)
Yarchoan et al, NEJM (2017)
24BP1209
Antibody-vaccine conjugate with improved vaccine delivery to
dendritic cells and immune induction
Anti-dendritic cell marker antibody
Neoantigen peptide vaccine
(BP1101)
ESMO 2021
1005P ”A new platform of personalized neoantigen cancer vaccines directed by
checkpoint inhibitor antibodies to improve cancer immunity.” Source: BrightPath
25BP1209 (cont’d)
Improves anti-tumor immunity by increasing cDC1’s uptake of
peptide vaccine and migration to lymph node
Dendritic cells’ uptake of vaccine
Immune induction in a mouse model and transition to lymph nodes
（B6 +MC38 neoantigen）
1.2
cDC1
cDC2
1500
Amount of vaccine transferred to
the lymph nodes (relative）
IFNg+/ CD8+ cell (%)
0.8
1000
0.4
500
cDC1
cDC2
cDC1
cDC2
0.0 0
Adj Adj+peptide Adj+peptide+CD40Ab
e
h)
h)
Antibody-binding
h)
h)
Antigen peptide
lin
2 Eq 2 Eq - - -
ig
ig
ig
ig
antigen peptide - 2 Eq 2 Eq
Sa
(h
(h
(FAM-labeled)
(h
(h
c
c
40
40
-F
nF
Non-binding
D
D
gk
- - 2 Eq 2 Eq -
k-
C
+C
antigen peptide Anti-DC marker mAb
- - 200
dp
g
+
dp
(μg/head)
c
Fc
A
-F
A
-n
gk
gk
PolyICLC
dp
Anti-DC marker mAb - 200 - 200 - 8
dp
A
(μg/head)
(ug/head)
A
PolyICLC
8 -
(μg/head)
Source: BrightPath
26BP1209 (cont’d)
Tumor-bearing mouse study demonstrated increased anti-tumor
immunity
Vaccine (OVA)
Day0 3 10 33
E.G7 (EL4/OVA)
OVA expressed lymph
Tumor cell transplant
2800
2400
2000 saline
Tumor size (mm3)
1600
adjuvant only
1200
Administration
800
Administration
vaccine ← BP1101 type
400
vaccine-binding
0 dendritic cell marker ← BP1209 type
0 7 14 21 antibody
Days after cancer cell transplant
Source: BrightPath
27BP1401
Lipid nanoparticle of Type-A TLR9 agonist
Suppress tumor growth by changing tumor immune-microenvironment
LNP enables intravenous administration expecting safely brought systemic
effects, which is differentiated from intratumoral injection-based predecessors in
a clinical stage
Promote cross presentation
of Class I antigen
Blood vessel
T cell
Enhancement of antigen-
presentation Lymph node
Recruit T cells to
BP1401 tumor site
TLR9 agonist
T cell
Cancer
antigen
Cancer cell
Cancer
Cancer antigen
Immune
checkpoint
Macrophage
Dead cancer cell
Myeloid cell, etc.
28BP1401(cont’d)
BP1401 promotes T-cells’ infiltration to and eradication of tumors
Intratumoral administration of BP1401
Predecessors under clinical development are
all intratumorally administrated 8 6 40
4000
** **
N o n -tre a te d **
R e la tiv e E x p r e s s io n
R e la tiv e E x p r e s s io n
R e la tiv e E x p r e s s io n
6 30
4
Is o ty p e -A b Non-treated D35LNP0.5
3000
4 * 20
T u m o r s iz e (m m )
3
C D 8 a -A b 2
2 10
D 35LNP+CD8Ab
0 0 0
2000 D 3 5 L N P 0 .5 %
10 2 .5 2 .0 50
** **
**
R e la tiv e E x p r e s s io n
R e la tiv e E x p r e s s io n
R e la tiv e E x p r e s s io n
R e la tiv e E x p r e s s io n
Cxcl11 Cxcr3
8 2 .0 40
1 .5
1000 6 1 .5 30
* s 4 1 .0
1 .0
20
0 .5
** **
2 0 .5 10
0
** ** **
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 0 0 .0 0 .0 0
Intravenous administration of BP1401
6 5 6
Ifna6 Ifnb1 Ifng
R e la tiv e E x p r e s s io n
R e la tiv e E x p r e s s io n
R e la tiv e E x p r e s s io n
N o n -tre a te d 4
4000 4 4
D 3 5 o n ly 3
Interferons **
** ** **
T u m o r s iz e (m m )
D 3 5 L N P 3 .0 %
3
2
2 2
3000
D 3 5 L N P 0 .5 % 1
0 0 0
2000 6 3 3 4
* i.v. Cxcl9 Cxcl10 Cxcl11 Cxcr3
R e la tiv e E x p r e s s io n
R e la tiv e E x p r e s s io n
R e la tiv e E x p r e s s io n
R e la tiv e E x p r e s s io n
3
4 2 2
1000
Chemokines ** 2
2
** 1 1
**
** 1
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 0 0 0 0
Intravenous administration of BP1401 in combo with anti-PD-1 mAb
800
Is o ty p e A b
g
tu m o r v o lu m e (m m )
D 3 5 L N P 0 .5 %
3
600
A n ti P D - 1 A b 800 600 * 200 150
400 C o m b in a tio n 600 * 150
400 100
c e lls /m g
c e lls /m g
c e lls /m g
c e lls /m g
400 100
200 200 50
* 200 50
**
0 0 0 0 0
0 5 10 15 20
day
Lipid nanoparticles of Type-A CpG D35 suppress tumor growth by changing tumor immune-microenvironment and activate CD8 T cells in mice
Journal of Controlled Release 313 (2019) 106-119
29BP1200
A novel antibody targeting CD73
Adenosine generation in tumors causes T cell exhaustion and dysfunction
CD73 is highly expressed in various tumors and produce adenosine, leading to
poor prognosis
Dendritic
T cell cell
CD8+ Production of adenosine in the tumor
T cell environment
CD4+
T cell
T cell
Cancer
antigen
Cancer cell
Tumor
Dendritic cell
Cancer antigen
Immune Suppress tumor cytotoxicity Promote differentiation into suppressor T cells
checkpoint
Dead cancer cell
30BP1200 (cont’d)
BP1200 blocks the function of adenosine-generating enzyme (CD73)
Superior to benchmarks in clinical stages
BP1200 promotes T cell division and cytokine secretion, which leads to
enhance anti-tumor immunity
• がん免疫を亢進し、抗腫瘍効果を発揮することが期待される
Induction of secretion of
Inhibition of adenosine-generating enzyme Promotion of T cell division
cytokine (IFN-γ)
● BP1200
〇 Control antibody
ESMO 2021
987P “A novel therapeutic antibody against CD73 that ameliorates the tumor
Source: BrightPath Biotherapeutics
microenvironment and improves the efficacy of cancer immunotherapy”
31BP1210
Targeting TIM-3 as a novel immune checkpoint following PD-1/L1
BP1210 blocks TIM-3 and inhibits exhaustion of T cell to enhance anti-tumor
immunity
BrightPath’s target immune checkpoints T cell exhaustion is associated with
increased TIM-3 expression
T cell
T cell
Dendritic
cell
Naive
T cell
Anti-
BP1210 CTLA-4
BP1210
Stem-like memory
PD-1lo T cell
Exhausted
(Exhausted)
PD-1med Anti-
LAG3+ PD-1
TIM-3+
CD39+
Hyper-exhausted
(Hyper-exhausted)
Cancer cell PD-1hi
Antigen presenting cell LAG3+
TIM-3+
CD39+
Red: Clinically validated, regulatory-approved target
Bold: BrightPath’s target Granzyme Cytotoxic T cell
32BP1210 (cont’d)
BP1210 promotes T cell proliferation and cytokine secretion
Superior to benchmarks in clinical stages
SEB stimulation of PBMC (in combination with PD-1 antibody)
T cell count IL-2 production IFN-γ production
(day6) (day 6) (day 2)
2.0×10 5 6000 15000
(pg/ml)
IFN-γ (pg/ml)
cell count
1.5×10 5
(pg/ml)
IL-2 (pg/ml) 4000 10000
TT細胞数
1.0×10 5
IFN-γ濃度
IL2濃度
2000 5000
5.0×10 4
0 0 0
体
体
体
抗
抗
s社
抗
s社
s社
0
0
0
ル
ル
ル
21
21
21
it i
it i
it i
ー
ー
ー
P1
P1
P1
ar
ar
ar
ロ
ロ
ロ
B
B
B
ov
ov
ov
ト
ト
ト
ン
ン
ン
N
N
N
コ
コ
コ
33BP1210 (cont’d)
BP1210 strongly inhibits the binding of ligand PtdSer to TIM-3
• Superior to benchmarks in clinical stages
BP1210 promotes T cell proliferation and cytokine secretion
• Superior to benchmarks in clinical stages
Binding inhibition of PtdSer SEB stimulation of PBMC (in combination with PD-1 antibody)
T cell count IL-2 production IFN-γ production
(day6) (day 6) (day 2)
2.0×10 5 6000 15000
(pg/ml)
IFN-γ (pg/ml)
cell count
1.5×10 5
(pg/ml)
IL-2 (pg/ml)
4000 10000
TT細胞数
1.0×10 5
IFN-γ濃度
IL2濃度
2000 5000
5.0×10 4
0 0 0
体
体
体
抗
抗
s社
抗
s社
s社
0
0
0
ル
ル
ル
21
21
21
it i
it i
it i
ー
ー
ー
P1
P1
P1
ar
ar
ar
ロ
ロ
ロ
B
B
B
ov
ov
ov
ト
ト
ト
ン
ン
ン
N
N
N
コ
コ
コ
Source: BrightPath Biotherapeutics
34BP1211
Anti-PVR antibody to inhibit binding TIGIT to PVR (CD155) and prevent T
cell exhaustion
BrightPath targeting immunocheckpoints
Inhibition of TIGIT binding
BP1211 BP1210
(PVR)
antibody concentration (log, μg/mL)
Red: Clinically validated, regulatory-approved target
Bold: BrightPath target Source: BrightPath
35BP1206
Anti-HLA-DR antibody targeting HLA-DR on blood cancer cells
Antitumor effects in vitro
dependent on HLA-DR expression
100 60,000
Cancer cell killing
80
HLA-DR expression (MFI)
Viable Cancer Cells (%)
40,000
60
40
20,000
20
0 0
MUTZ-5 (ALL)
L428 (HL)
GRANTA-519 (DLBCL)
JJN-3 (MM)
Rmos (BL)
OCI-LY-19 (DLBCL)
Pfeiffer (DLBCL)
Daudi (BL)
Raji (BL)
Mino (MCL)
KG-1 (AML)
KMS-11 (MM)
KMS-26 (MM)
NU-DHL-1 (DLBCL)
Nalm-6 (ALL)
Kasumi-１ (AML)
BP1206 induces HMGB1(DAMP) release from dying cancer cells
Control BP1206
Source: BrightPath HMGB1 in tumor
36BP1206: (cont’d)
BP1206 exhibits robust antitumor effects in vivo
NOG mouse
Day -12 0 42
Hodgkin’s lymphoma cell L428
s.c. engraftment (n=10)
10 mg/kg i.p. Q4D x 4 times
1200
1400 PBS
Isptype (10mg/kg)
3 complete
BP1206 (1mg/kg) 1000 eliminations
1200
BP1206 (5mg/kg)
BP1206 (10mg/kg) BP1206 10mg/kg
tu m o r w e ig h t ( m g )
1000 800
Mouse # 47
Tumor size( mm3)
800
600
BP1206 10mg/kg
BP1206 Mouse # 52
600
400
400
BP1206 10mg/kg
Mouse # 53
200
200
0 0
Is o ty p e 1 m g /k g 5 m g /k g 1 0 m g /k g
-7 0 7 14 21 28 35 42
Days post tumor engraftment
Source: BrightPath 37Company Overview
Company Profile
Company
BrightPath Biotherapeutics Co., Ltd. (Tokyo Stock Exchange Mothers: 4594)
name
Headquarters: 2-2-4 Kojimachi, Chiyoda-ku, Tokyo
Location Kawasaki Research Laboratories: 3-25-22 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa
Cell Technology Laboratories: 3-25-22 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa
Established May 8, 2003
Business
Development of novel cancer immunotherapy
description
Stated capital 6,459 million yen (as of the end of March 2021)
Number of
44 (as of the end of March 2021)
employees
Chief Executive Officer Kenichi Nagai
Chief Science Officer Norihiro Nakamura
Director (part-time) Akira Yamada (Professor at Kurume University)
Management Director (outside, independent ) Hirotaka Takeuchi (Professor at Harvard Business School)
team
Auditor (outside) Tsutomu Kishino
Auditor (outside, independent) Taketoshi Abe
Auditor (outside) Yoshiyasu Yamaguchi (Partner, TMI Associates)
39Business Locations
Headquarters:
Kojimachi Central Building 7F,
2-2-4 Kojimachi, Chiyoda-ku,
Tokyo, Japan
Kawasaki Research Laboratories
Cell Technology Laboratories
Life Innovation Center, 3-25-22 Tonomachi, Kawasaki-ku,
Kawasaki, Kanagawa, Japan
Haneda Airport
Tonomachi International
Strategic Zone
King SkyFront
神奈川県川崎市川崎区殿町3丁目25
ライフイノベーションセンター412
電話 044-440-3310
FAX 044-440-3311
40We pioneer immunotherapy, to enable a world where cancer patients can defeat cancer on their own.
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