cstone pharmaceuticals (2616.hk) company …
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CSTONE PHARMACEUTICALS (2616.HK)
COMPANY PRESENTATION
January 2021
2
Presentation Disclaimer
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The information in this presentation has been prepared by representatives of CStone Pharmaceuticals (the "Company" and, together with its subsidiaries, the "Group") for
use in presentations by the Group for information purpose. No part of this presentation will form the basis of, or be relied on in connection with, any contract or commitment
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Certain statements contained in this presentation and in the accompanying oral presentation, may constitute forward-looking statements. Examples of such forward-looking
statements include those regarding investigational drug candidates and clinical trials and the status and related results thereto, as well as those regarding continuing and
further development and commercialization efforts and transactions with third parties. Such statements, based as they are on the current analysis and expectations of
management, inherently involve numerous risks and uncertainties, known and unknown, many of which are beyond the Company’s control. Such risks include but are not
limited to: the impact of general economic conditions, general conditions in the pharmaceutical industry, changes in the global and regional regulatory environment in the
jurisdictions in which the Company’s does business, market volatility, fluctuations in costs and changes to the competitive environment. Consequently, actual future results
may differ materially from the anticipated results expressed in the forward-looking statements. In the case of forward-looking statements regarding investigational drug
candidates and continuing further development efforts, specific risks which could cause actual results to differ materially from the Company’s current analysis and
expectations include: failure to demonstrate the safety, tolerability and efficacy of the Company’s drug candidates, final and quality controlled verification of data and the
related analyses, the expense and uncertainty of obtaining regulatory approval, the possibility of having to conduct additional clinical trials and the Company’s reliance on
third parties to conduct drug development, manufacturing and other services. Further, even if regulatory approval is obtained, pharmaceutical products are generally
subject to stringent on-going governmental regulation, challenges in gaining market acceptance and competition. These statements are also subject to a number of material
risks and uncertainties that are described in the Company’s prospectus published onto the websites of the Company and The Stock Exchange of Hong Kong Limited and
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3
Table of Contents
1 Introduction 4
2 Clinical Progress Overview 14
3 CStone Pipeline 2.0 Advancement 28
4 Full-fledged Biopharma Capabilities 32
4
Introduction
5Note: NDA = New Drug Application
Industry-leading
management team
Integrated
biopharma with clear focus
on clinical development, fast
ramp-up of manufacturing
capability, and transitioning
into commercial stage
$150M
Series A(July 2016)
$262M
Series B(May 2018)
$328M
HK IPO(Feb 2019)
Well-balanced
oncology portfolio with a focus
on immuno-oncology and
precision medicine with 5+ NDA
submissions in 2020
$200M
Pfizer strategic investment(Sep 2020)
To become a world-renowned biopharmaceutical company that is
leading the way to conquering cancer
5 Years Since Company
Inception
HKEx listed
2616.HK
6
Industry leading management team with proven track
record and complementary expertise
Shirley Zhao, MD, MBA
Greater China GM,
Head of Commercial
Frank Jiang, MD, PhDChairman, Chief Executive Officer
Jason Yang, MD, PhD
Chief Medical Officer
Archie Tse, MD, PhD
Chief Scientific Officer
Jingrong Li, PhD
Chief Technology Officer
Sanhu Wang, MPH
SVP, Government and
Regulatory Affairs
7
Clinical development engine: strong in-house team led by
experienced leaders and supported by global CROs
7
▪ Former SVP and Head of Clin Dev for Beigene, led development of PD-1, BTK, PARP and RAF dimer inhibitors
▪ Led 40+ global and China trials
Jason Yang, MD, PhD
CMO
▪ Former Executive Director of Early Clin Dev at
MSD (US)
▪ Led 30+ FIH oncology trials
▪ Led 20+ I/O combination trials
Archie Tse, MD, PhD
CSO
▪ Former Head of APAC R&D for Sanofi
▪ Led a 21,000 patient mega-trial
▪ Led 79 clinical trials and 30 NDAs
within five years
Frank Jiang, MD, PhD
Chairman and CEO
Keep clinical strategy planning & development oversight in-house, while outsourcing day-to-day
execution to global CROs to ensure optimal balance between efficiency and scalability
Clin
ica
l
De
ve
lop
me
nt &
PV
1
Clin
ica
l
Op
era
tio
ns
Bio
me
tric
s &
Me
dic
al W
ritin
g
Qu
alit
y
Assu
ran
ce
Responsible for late-stage clinical
development and regulatory affairs
Ea
rly
De
ve
lop
me
nt
Clin
ica
l
Ph
arm
aco
logy
Tra
nsla
tio
nal
Me
dic
ine
&
Bio
ma
rke
r
Mo
lecu
lar
Dia
gn
ostics
Responsible for early-stage clinical
development and diagnostics/biomarkers
Strong in-house team with ~160 clinical staff, representing ~30% of total employees, of which ~70%
hold advanced degrees2 and ~70% have clinical development experience at MNCs
Note: 1. Includes GI cancer, lung cancer, hematology & other solid tumors, and pharmacovigilance. 2.Master and above
8
Distinguished world-class scientific advisory board with
deep oncology and IO expertise
Note: ASCO = American Society of Clinical Oncology; AACR = American Association for Cancer Research.
Paul Bunn
MD
Weiping Zou
MD, PhD
Richard Finn
MD
Former AACR President
2018-2019
Professor of Oncology,
Johns Hopkins
University
Chair, AACR Cancer
Immunology
Charles B.de Nancrede
Professor,
University of Michigan
Former International
Liver Cancer
Association President
Clinical Professor,
UCLA
Elizabeth Jaffee
MD
Former ASCO President
2002-2003
Distinguished Professor,
University of Colorado
9
Well-balanced oncology portfolio of 14 innovative assets
focused on immuno-oncology and precision medicine
9
Source: Company
Note: Assets status denote progress in the region noted in the column titled “Rights”.
* CStone obtains the exclusive global right to lead development and commercialization of LCB71 outside the Republic of Korea
POC = Proof of Concept, AML= Acute Myeloid Leukemia, AdvSM = Advanced Systemic Mastocytosis, ISM = Indolent Systemic Mastocytosis, GIST = Gastrointestinal Stromal Tumor, HCC =
Hepatocellular Carcinoma, ISM = Indolent Systemic Mastocytosis, NKTL = Natural KILLER/T Cell Lymphoma, NSCLC = Non-small Cell Lung Cancer, MTC = Medullary Thyroid Cancer, R/R =
Relapsed or Refractory, SM = Systemic Mastocytosis, MM = Multiple Myeloma.
Drug Candidate
Lead Indication(s)
and Line(s) of
Therapies
Rights Pre-clinicalDose
EscalationPOC Pivotal NDA Partner
Pralsetinib
(RET)
1L / 2L NSCLC,
1L MTC
Avapritinib
(KIT / PDGFRA)
PDGFRA exon 18 GIST,
AdvSM, ISM
Ivosidenib
(IDH1)
R/R AML, 1L AML,
Cholangiocarcinoma
Sugemalimab
(CS1001, PD-L1)
NSCLC, GC, EC
R/R NKTLOut-licensed
CS1003
(PD-1)HCC
Fisogatinib
(FGFR4)1L / 2L HCC
CS1002
(CTLA-4)Solid tumors
CS3002
(CDK4/6)Solid tumors
CS3005
(A2aR)Solid tumors
NM21-1480
(PD-L1/4-1BB/HSA)Solid tumors
CS5001/LCB71
(ROR1)
Solid tumors,
hematologic cancers
Multi-Specific #2 Undisclosed
Multi-Specific #3 Undisclosed
ADC #2 Undisclosed
Pre
-cli
nic
al
La
te-s
tag
eC
lin
ical/
IND
Taiwan and Singapore NDA submission
Mainland China and Taiwan NDA submission
Mainland China Ex-Greater China
Ex-Greater China
ChinaGlobal Korea Singapore
Mainland China NDA submission
Mainland China NDA submission
*
10
Partnering with and recognized by Pfizer through
strategic and multi-dimensional collaboration
Co-development of
Pfizer’s assets
Joint in-licensing of global
innovative drugs
China commercialization of
sugemalimab
Equity investment: $200mm (at approximately HK$13.37 per share)
Long-term collaboration
solidified through equity
investment
Competitive platform for in-
licensing deals to allow
rapid expansion of pipeline
Faster and broader
commercialization of
sugemalimab in China
Synergistic Collaboration
Pfizer
◼ A global pharmaceutical leader with
prestigious brand value
◼ Extensive commercialization
network in China
◼ Leading oncology franchise with
robust pipeline of drug candidates
CStone
◼ An emerging leader in the
biopharmaceutical industry in China
◼ Sugemalimab, a commercial-ready,
potential best-in-class PD-L1 asset
for large indications
◼ Superior clinical capabilities with
strong execution
In addition to the equity investment
premium, CStone is entitled to receive
▪ Up to $280mm in milestone
payments, and
▪ Tiered, mid-to-high teens royalties
▪ Post proof-of-concept oncology
assets
▪ CStone to receive low double-
digit royalties
▪ Jointly in-license for Greater China
market
▪ CStone retains an option to
participate in co-promotion
1 2 3
11
Partnering with and recognized by EQRx, a global top-
notch biotech, through significant license-out transaction
Meaningful
immediate financial
benefits
Maximize global
commercial potential of
two lead I/O assets
▪ EQRx’s innovative model to position CStone’s assets competitively in large indications such as
NSCLC
▪ EQRx’s exceptionally experienced “all-star” team with stellar track record of success
▪ Broad potential to pursue CS1003 drug combos for the China market
▪ Immediate and significant capital proceeds to invest in strategic initiatives, as we transition into a
fully integrated biopharma and pursue CStone Pipeline 2.0 strategy
Capability of
forming global
partnership
▪ Continue to build on the successful track record of forming strategic partnership
▪ Elevate CStone as a partner of choice for global biotech and biopharma
Importance for
patient community
▪ Make CStone’s assets available to global patient community
▪ EQRx’s innovative business model to enlarge access and make drugs more affordable for patients
CStone to out-license ex-China rights to EQRx for two key late-stage
assets, sugemalimab (PD-L1) and CS1003 (PD-1)
▪ EQRx will lead clinical development and commercialization of these
two assets outside of Greater China
▪ CStone to receive US$150m upfront payment, up to US$1.15bn
milestone payments and tiered royalties on net sales
12
We are advancing Pipeline 2.0 development with
multiple first-in-class / best-in-class molecules
▪ We have secured the global rights for multiple innovative molecules with first-in-class / best-in-class potential
▪ Starting from multi-specific molecules and ADCs, our portfolio is well positioned to advance towards Pipeline 2.0
1 NM21-1480
(PD-L1 x 4-1BB x HSA)
• Rights in Greater China, Korea and
Singapore
• Tri-specific molecule with the
potential to be BIC molecule as the
next generation PD-(L)1 inhibitor
• In-licensed from Numab
3 Multi-Specific #3
1 LCB71 (ROR1 ADC)
2 Multi-Specific #2
2 ADC #2
• Global rights
• Global FIC
• Nominated and designed by
CStone
• Global rights (outside Korea)
• Potentially a BIC ROR1 ADC with
differentiated technology
• In-licensed from LegoChem
• Global rights
• Global FIC
• Nominated and designed by
CStone
• Global rights
• Potentially a BIC molecule
• Nominated and designed by CStone
Multi-specific
molecules
ADC
And more…
And more…
Others And more…
13
Clear strategy towards building a full-fledged commercial
organization with near-term ambitions to reach “critical mass”
Note: I/O = immuno-oncology; EAP = early access program
Reach “Critical Mass” with
strong commercial platform
▪ Oncology focused portfolio with 3+
precision medicine and multiple I/O
combos
▪ Well-established sales team with
broad hospital coverage in China
▪ EQRx to maximize commercial value of
sugemalimab and CS1003 in ex-China
▪ Continue to explore potential
partnership with global partners for
value creation, with ex-China rights in
hand
Achieve “Global Vision”:
▪ To become globally recognized as
the leading Chinese biopharma
Stage 1 (2020)
Stage 2 (in 3-5 years)
Stage 3 (beyond)
Develop “Full-Fledged”
commercial organization
• Commercial organization with
core competencies and team
ready by year-end of 2020
• Focus on launching precision
medicines. Initiated Bo’ao EAP
precision medicine pilot program
in Hainan
14
Clinical Progress Overview
15
Note:
AML= Acute Myeloid Leukemia,, cHL= Classical Hodgkin’s Lymphoma, GIST = Gastrointestinal Stromal Tumor, HCC = Hepatocellular Carcinoma,
ENKTL = Extranodal Natural KILLER/T Cell Lymphoma, NSCLC = Non-small Cell Lung Cancer, EC = Esophagus Cancer, MTC = Medullary Thyroid
Cancer, R/R = Relapsed or Refractory
Significant clinical progress up to date
30 clinical trials with 17 registrational trials by 2021
Sugemalimab
(PD-L1)
CS1003
(PD-1)
Ivosidenib
(IDH1)
Avapritinib
(KIT/PDGFRA)
Pralsetinib
(RET)
• 2L NSCLC• Mainland China NDA accepted in 2020 with priority review designation
• Taiwan NDA filing expected in 2021
• 1L NSCLC • Last patient in by 2020 and mainland China NDA filing expected in 2021
• 1L MTC• Last patient in and breakthrough therapy designation granted by 2020,
mainland China NDA filing expected in 2021
• PDGFRA exon 18 GIST• Mainland China NDA accepted in 2020 with priority review designation
• Taiwan NDA filed in 2020
• R/R AML• Singapore NDA filed in 2020
• Last patient in by 2020 and mainland China NDA filing expected in 2021
• 1L AML • Patient enrollment on track
• 1L Stage IV NSCLC • Mainland China NDA accepted in 2020
• Stage III NSCLC • Last patient in by 2020 and mainland China NDA filing expected in 2021
• 1L GC • Patient enrollment on track
• 1L ESCC • Patient enrollment on track
• R/R ENKTL • Patient enrollment on track
• 1L HCC • Patient enrollment on track
Indication Status
16
Significant clinical progress – pralsetinib (RET) Global and China development and regulatory status
U.S.
Greater China
Registrational Potential Study
PartnerDrug
CandidateIndications Region
Mono
/ComboStudy Initiation
Patient
EnrollmentNDA Submission NDA Approval
Pralsetinib
(RET)
NSCLC 2L China Mono
MTC 1L China Mono
NSCLC 1L China Mono
Basket cohort China Mono
Joining global study
Joining global study
Joining global study
Joining global study
PartnerDrug
CandidateTarget Indications
Pivotal / Registrational Trial
Patient Target Enrollment
U.S. NDA
Submission
U.S. NDA
Approval
Pralsetinib RET
NSCLC * **
TC/MTC **
Achieved
Registrational StudyNote:
* Phase 3 AcceleRET Lung trial is ongoing
** In collaboration with Roche. Blueprint Medicines and Roche have co-exclusive rights to develop and commercialize pralsetinib in the U.S.
GAVRETOTM (pralsetinib) was granted accelerated approval by the FDA for the treatment of three indications: adult patients with metastatic RET fusion-positive NSCLC as detected by an FDA approved
test, adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant MTC who require systemic therapy, and adults and pediatric patients 12 years of age and older with
advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). Blueprint Medicines, GAVRETO
and associated logos are trademarks of Blueprint Medicines Corporation.
NDA = New Drug Application, NSCLC = Non-small Cell Lung Cancer, TC = Thyroid Cancer, MTC = Medullary Thyroid Cancer
17
Pralsetinib: potentially first-in-class RET inhibitorTargeted therapy with significant indication expansion potential
Broad and Durable Antitumor Activity in Patients with RET Fusion+ NSCLC
Total Newly Diagnosed Incidences in China (2020)
Source: Globocan 2020; CStone analysis;
Pralsetinib ASCO 2020 Presentation
Active Clinical Programs
In Partnership With
Not for promotional use.
ARROW
Note: ORRs are for response-evaluable patients.
Top-line data from the Phase 1/2 ARROW trial in patients with RET fusion NSCLC. Data cutoff date: November 18, 2019.
1. Two responses pending confirmation. 2. All responses confirmed.
Safety Summary
◼ Safety results (N=354; 400 mg
QD, all tumor types) were
consistent with prior data; most
reported AEs were grade 1 or 2;
no treatment-related grade 5 AEs
were reported.
◼ Overall, 4% of patients
discontinued treatment due to a
treatment-related AE.
ORR1: 61% (RET-fusion NSCLC
with prior platinum chemotherapy)
ORR2: 73% (RET-fusion NSCLC
with no prior systemic therapy)
ALL NSCLC PATIENTS (400 MG QD)
PER CENTRAL RADIOLOGY
Total Incidences:
80,832
Cancer Types Harboring RET Mutation
2X Breakthrough Therapy Designation
Orphan Drug Designation
Priority Review
Accelerated Approval
18
Significant clinical progress – avapritinib (KIT/PDGFRA) Global and China development and regulatory status
PartnerDrug
CandidateTarget Indications
Pivotal / Registrational Trial
Patient Target Enrollment
U.S. NDA
Submission
U.S. NDA
Approval
Avapritinib KIT/PDGFRA
PDGFRA exon 18
GIST
Advanced SM
Indolent SM Ongoing
Achieved
U.S.
Greater China
PartnerDrug
CandidateIndications Region
Mono
/ComboStudy Initiation
Patient
EnrollmentNDA Submission NDA Approval
Avapritinib
(KIT/PDGFRA)
PDGFRA
exon 18 GISTTaiwan Mono
PDGFRA
exon 18 GISTChina Mono
Advanced SM China Mono Exploring trial waiver
Indolent SM China Mono Exploring trial waiver
Registration with US NDA data
Note: AYVAKIT™ (avapritinib) is approved by the U.S. FDA for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations
Blueprint Medicines, AYVAKIT and associated logos are trademarks of Blueprint Medicines Corporation.
(1) Sufficient enrollment has been achieved to enable interim analysis and supplemental NDA filed in Q4 2020 in the U.S.
GIST = Gastrointestinal Stromal Tumors, SM = Systemic Mastocytosis
Registrational Study
(1)
Bridging study
19
Avapritinib: potentially first-in-class KIT/PDGFRA inhibitor Targeted therapy with significant indication expansion potential
Robust Clinical Activity Shown in NAVIGATOR Registrational Phase 1 Study
Fast Track Review
3X Breakthrough Therapy Designation
Priority Review
Total Newly Diagnosed Incidences in China (2020)
Source: Globocan 2020; CStone analysis; Avapritinib
ESMO 2020 Presentation Active Clinical Programs
Cancer Types Harboring PDGFRA exon 18
and/or KIT exons 9/11/13/14/17 mutations
In Partnership With
Total Incidences:
38,589
Not for promotional use.
Efficacy Summary
◼ ORR: 91% for all doses
◼ mDOR with avapritinib 300/400 mg: 22
months (95% CI, 14–NR); mPFS: 24
months (95% CI, 18–NR); mOS: not
reached
Safety Summary
◼ Most AEs were grade 1 or 2, with a lower
incidence of commonly reported AEs in
the 300 mg QD dose group compared
with the 400 mg QD dose group.
◼ No treatment-related grade 5 AEs were
reported.
Data cut-off: March 9, 2020. Long-term efficacy, tolerability and overall survival in patients with unresectable or metastatic PDGFRA D842V-
mutant gastrointestinal stromal tumor treated with avapritinib: NAVIGATOR phase 1 trial update. 2020 ESMO Virtual Congress
Orphan Drug Designation
Approval for PDGFRA exon 18 mutant GIST
PFS of Avapritinib in PDGFRA exon 18 mutant GIST
20
Significant clinical progress – ivosidenib (IDH1) Global and China development and regulatory status
Partner Drug Candidate Target IndicationsPivotal / Registrational Trial
Patient Enrollment
NDA
SubmissionNDA Approval
Ivosidenib IDH1
R/R AML
IC-Ineligible 1L AML
monotherapy
IC-Eligible 1L AML
combo with 7+3
IC-Ineligible 1L AML
combo with AZA
2/3L Cholangiocarcinoma
monotherapy
Achieved
PartnerDrug
CandidateIndications Region
Mono
/ComboStudy Initiation
Patient
EnrollmentNDA Submission NDA Approval
Ivosidenib
(IDH1)
IDH1m R/R AML Taiwan Mono
IC-Ineligible 1L
AML
combo with AZA
China Combo
IDH1m R/R AML China MonoIncluded in the list of drugs of urgent
clinical needs in mainland China
IDH1m R/R AML Singapore Mono
Joining global study
Registration with US NDA data
Bridging study
Global
Greater China and Singapore
Note: AML= Acute Myeloid Leukemia, R/R = Relapsed or Refractory, IC = intensive chemotherapy, AZA = azacytidine; 7+3 is a chemotherapy regimen for AML, where “7” refers to Cytarabine given daily
for 7 days and “3” refers to Daunorubicin given daily for 3 days
Registration with US NDA data
Registrational Study
21
TIBSOVO®: global first-in-class IDH1 inhibitor No immediate competitor in China; significant indication expansion potential
Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML
Fast Track Review
2X Breakthrough Therapy Designation
Priority Review
Total Newly Diagnosed Incidences in China (2020)
Source: Globocan 2020; CStone analysis Active Clinical Programs
AML Chondro
-sarcomaMDSiCCA CRC Prostate B-ALL Melanoma GBM LGG
Cancer Types Harboring IDH1 Mutation
Total Incidences:
34,151
In Partnership With
0 2 4 6 8 1 0 1 2 1 4 1 6 1 8 2 0 2 2 2 4 2 6 2 8 3 0 3 2 3 4 3 6 3 8 4 0
0 .0
0 .1
0 .2
0 .3
0 .4
0 .5
0 .6
0 .7
0 .8
0 .9
1 .0
O v e ra ll s u rv iv a l (m o n th s )
Su
rviv
al
pro
ba
bil
ity
N u m b e r o f p a t ie n ts a t r is k :
N o n -re s p o n d e rs
57 50 32 16 45757 43 25 11 456 215 47 3
N o n -C R /C R h re s p o n d e rs
C R + C R h
C R + C R h
N o n -C R /C R h re s p o n d e rs
N o n -re s p o n d e rs
O ve ra ll
12 1
18 10 3 11517 6 214 0
1 0 4 29 9 35577 15 6 038 2
C e n s o re d
Not for promotional use.
Orphan Drug Designation (R/R AML, CCA, GBM and MDS)
Approval for R/R AML and IC-Ineligible 1L AML
22
Asset overview
Note: as of Dec 31, 2020, including patients dosed with placebo
DLT = dose limiting toxicity, MTD = maximum tolerated dose, ADA = anti-drug antibodies, IgG4 = Immunoglobulin G4, ADCP = Antibody-Dependent
Cellular Phagocytosis, ADCC = Antibody-Dependent Cell-Mediated Cytotoxicity, CDC = Complement Dependent Cytotoxicity, EC = Esophageal Cancer
■ Fully-human, full length IgG4 derived from Ligand’s OmniRat® platform – minimal
possibility of generating ADA;
■ The only PD-L1 antibody that naturally lacks ADCC/CDC activity – better safety and
avoid unwanted attack of T cells;
■ Retains ADCP activity that potentially induces direct tumor killing by macrophages
and enhances tumor antigen presentation for long-term anti-tumor immunity – more
efficacious in certain indications like NKTL
Significant clinical progress – sugemalimab (PD-L1) (1/4)
Unique design
Prominent
safety profile
Best-in-class
potential
Significant
development
progress
■ Early phase studies demonstrated that Sugemalimab was safe & well tolerated
‒ No DLT1 from 3 mg/kg to 40 mg/kg, MTD2 not reached
‒ No infusion reactions; low ADA3 rate
‒ Low frequency of severe irAEs
■ Data showed potential of best-in-class PD-L1
‒ Encouraging anti-tumor activities observed in phase Ia dose-escalation study,
multiple phase Ib cohorts, phase II and phase III studies
‒ In particular, promising data in NSCLC, ESCC and NKTL
■ >1,600 patients dosed, with 5 registration trials ongoing, including 1 pivotal Ph II
study and 4 Ph III studies*
■ Strategically targeting China prevalent cancers including S3 and S4 NSCLC, GC and
ESCC
23
Significant clinical progress – sugemalimab (PD-L1) (2/4)
Note: cross trial comparison subject to the usual caveat; NDA status as of Jan 22nd, 2021; mNSCLC = metastatic non-small cell lung cancer, sq = squamous, nsq = non-squamous
* PFS HR data of POSEIDON trial not publicly available
Source: public information and CStone analysis
48
46
44
29
67
0 10 20 30 40 50 60 70
Tislelizumab (sq, RATIONALE 307)
Sintilimab (sq, ORIENT-12)
Pembrolizumab (sq, Keynote-407)
Atezolizumab (sq, IMpower 131)
Durvalumab (sq, POSEIDON)*
Sugemalimab (sq, GEMSTONE-302)
PD-(L)1 for 1L
treatment of
mNSCLC
(sq)
PD-L1 PD-1
▪ Potentially the most efficacious PD-(L)1 for first line treatment of mNSCLC (sq)
▪ Potentially the best-in-class PD-L1 for first line treatment of mNSCLC
PD-(L)1 for 1L
treatment of
mNSCLC
(sq & nsq)
NDA StatusReduction of the Risk of Disease Progression or Death (%)
Under review
Not approved
Not approved
Approved
Under review
Approved
36
48
52
46
39
48
44
40
36
29
50
0 10 20 30 40 50 60
Tislelizumab (nsq, RATIONALE 304)
Tislelizumab (sq, RATIONALE 307)
Sintilimab (nsq, ORIENT-11)
Sintilimab (sq, ORIENT-12)
Camrelizumab (nsq, SHR-1210-303)
Pembrolizumab (nsq, Keynote-189)
Pembrolizumab (sq, Keynote-407)
Atezolizumab (nsq, IMpower 132)
Atezolizumab (nsq, IMpower 130)
Atezolizumab (sq, IMpower 131)
Durvalumab (sq&nsq, POSEIDON)*
Sugemalimab (sq&nsq, GEMSTONE-302) Under review
Not approved
Not approved
Approved
Not approved
Approved
Approved
Approved
Under review
Under review
Approved
Under review
24
Significant clinical progress – sugemalimab (PD-L1) (3/4)Phase Ib study data in 1L ESCC and Phase II study data in rr-ENKTL
Source: Company, ESCC Ph Ib data presented at 2020 ESMO, rr-ENKTL Ph II data presented at 2020 CSCO
Note: PTCL = peripheral T-cell lymphoma; HDAC = histone deacetylase; ORR = Overall Response Rate; DOR = Duration Of Response;
Sugemalimab + CF (Cisplatin + 5 FU) in 1L ESCC
ORR = 67.6% (25/37), DCR = 89.2% (33/37)
Sugemalimab as monotherapy in rr-ENKTL
ORR = 44.7% (17/38), CR = 31.6% (12/38)
mDOR = 16.8 months, 1 Yr OS rate: 55.5%
Sugemalimab SintilimabChidamide
(Approved in rr-PTCL, China, 2014)
Class PD-L1 PD-1 HDAC
Study CS1001-201 ORIENT-4 Registration Study Real World Study
n 38 28 16 33
CR 31.6% (12/38) 7.1% (2/28) 6.3% (1/16) 6.1% (2/33)
DOR (m)16.8
(1.0,16.8+)
4.1
(0+,4.2+)UNK UNK
Source CSCO 2020 ASCO 2019 Ann Oncol, 2015[4] J Hematol Oncol,
2017[5]
31.6
7.1 6.3 6.1
0
10
20
30
40
CR
(%
)
ime on reatment ays
atients
CR R
R
CR RS reatment ngoing anti cancer therapy eath
ORR*: 67.6% (25/37)
DCR: 89.2% (33/37)
DOR: not reached
Sugemalimab TislelizumabDurvalumab+
Tremelimumab
Class PD-L1 PD-1 PD-L1
n 37 15 6
ECOG0: 20.5%
1: 79.5%
0: 26.7%
1: 73.3%
0: 0%
1: 100%
Chemo
RegimenCF CF CF
DOR (m)NR
(0.03+~13.3+)12.8 Not reported
Source ESMO 2020 CSCO 2019 ASCO GI 2019
67.6
46.7
33.3
0
20
40
60
80
OR
R (
%)
* 20 confirmed PR; 5 PR to be confirmed as of data cut-off on 19 February 2020
25
Sugemalimab + XELOX (Capecitabine
+ Oxaliplatin) in 1L GC/GEJ (Gastric or
Gastroesophageal Junction
Adenocarcinoma)
* 17 confirmed PR; 1 PR to be confirmed as of data
cut off on 19 February 2020
Best Response
Partial Response (PR)
Stable Disease (SD)
Progressive Disease (PD)
30% Shrinkage
ORR*: 62.1% (18/29)
DCR: 82.8%
DOR: 11.3m
Target Lesion Shrinkage from Baseline
Change (
%)
to B
aselin
e
Sugemalimab (PD-L1) as monotherapy
in CC/GBC (Cholangiocarcinoma or
Gallbladder Carcinoma)
* 2 confirmed PR; 1 PR to be unconfirmed as of data
cut-off on 1 July 2019
Target Lesion Shrinkage from Baseline
Change (
%)
to B
aselin
e30% Shrinkage
ORR*: 10.3% (3/29)
DCR: 37.9%
DOR: 5.39m
Sugemalimab (PD-L1) as monotherapy
in MSI-H/dMMR Cancer
Pancreatic*
30% Shrinkage
Intestinal*
** Unless specified, all patients were Colorectal Cancer
Best Response
Partial Response (PR)
Stable Disease (SD)
Progressive Disease (PD)
Best Response
Partial Response (PR)
Stable Disease (SD)
Progressive Disease (PD)
ORR*: 38.1% (8/21)
DCR: 57.1%
DOR: not reached
Target Lesion Shrinkage from Baseline
Significant clinical progress – sugemalimab (PD-L1) (4/4)Phase Ib study data: other cohorts
Change (
%)
to B
aselin
e
62.1
48.6
60
68.4 66.7
85
0
10
20
30
40
50
60
70
80
90
OR
R (
%)
CS1001Keytruda
(062)
Keytruda
(059)Opdivo
Camrelizu
mabSintilimab
Class PD-L1 PD-1 PD-1 PD-1 PD-1 PD-1
n 29 257 vs 250* 25 38 48 20
ECOG0: 41.4%
1: 58.6%
0: 46.0%
1: 54.0%
0: 60.0%
1: 40.0%
0: 50.0%
1: 50.0%
0: 41.7%
1: 58.3%
0: 45.0%
1: 55.0%
Regimen XELOXCisplatin + 5-
FU or
Capecitabine
Cisplatin + 5-
FU or
Capecitabine
SOX or
XELOXXELOX XELOX
DOR (m)11.3
(1.0+ ~14.1+)6.8
4.6
(2.6 ~ 20.3+)
9.9
(5.8, NR)NR
5.3
(4.8~7.2)
Source ESMO 2020 ASCO 2019 ESMO 2017
Ann Oncol.
2019 Feb
1;30(2):250-
258
ASCO
2019ASCO 2019
26
Str
ate
gic
va
lue
Ph
I D
ata
Hig
hli
gh
tsA
ss
et
ove
rvie
wSignificant clinical progress – CS1003 (PD-1) & CS1002 (CTLA-4) Two Additional I/O Backbones: preliminary data and development strategy
DLT: dose-limiting toxicity;MTD: maximum tolerated dose; Q3W: once every 3 weeks; PK: pharmacokinetics; ADA: anti-drug antibody; PR: partial response; VEGF: vascular endothelial growth factor; TKI:
tyrosine kinase inhibitor; HCC: hepatocellular carcinoma
1=Squamous cell carcinoma of the cervix; 2=Synovial sarcoma; 3=Hepatocellular carcinoma;4=Gastric adenocarcinoma; 5=Leiomyosarcoma; 6=Malignant melanoma; 7= Leiomyosarcoma; 8=
Fibromatosis; 9= Follicular dendritic cell sarcoma; 10=Uterine Leiomyosarcoma; 11= Laryngeal squamous cell carcinoma; 12= Oesophageal squamous cell carcinoma; 13= Oesophageal squamous cell
carcinoma.
■ A full-length, fully human IgG1 mAb against CTLA4
■ Amino acid sequence identical to ipilimumab (Yervoy)
■ CS1002 monotherapy was well tolerated up to 10 mg/kg
Q3W, with no DLT and no MTD reached (N=13)
■ CS1002 demonstrated dose-proportional PK; increase in
absolute lymphocyte count (ALC) observed indicating
target engagement
■ Overall clinical profile is consistent with that of ipilimumab
CS1002
■ Potentially become another outstanding CTLA-4 inhibitor
after Ipilimumab, which has not been launched in China
■ One of 3 I/O backbones to enable flexible combo strategy,
including chemo-free I/O-I/O combo with CS1003
CS1002 induced early ALC increase, similarly to Ipilimumab
CS1003
■ Humanized IgG4 anti-PD-1 mAb
■ Recognize both human & murine PD-1 with unique
advantage to evaluate efficacy in syngeneic mouse
models, esp. for testing combinations with small molecules
■ Bridging Ph I conducted in China showed that CS1003
monotherapy was safe and tolerable at 60mg and 200mg
Q3W; no DLT or MTD was observed (N=19)
■ Ph Ib data showed that ORR and mPFS reached 40%
and 8.4 months respectively among 20 patients that
received the treatment of CS1003 + lenvatinib
■ One of 3 I/O backbones with multiple combo studies
ongoing, including the combo study of CS1003 + CS1002
and the global randomized Ph III trial of CS1003 +
lenvatinib in first line treatment for advanced
unresectable HCC (CS1003-305)
Preliminary efficacy of CS1003 + lenvatinib in HCC
1 mg/kg (N=6) 3 mg/kg (N=3) 10 mg/kg (N=4) 10 mg/kg
CS1002 Ipilimumab
27
Progress on other clinical-stage assets
CS3002
(CDK4/6)
◼ Conducting a Ph I trial for solid tumors as monotherapy in Australia/China
CS3005
(A2aR)
◼ Conducting a Ph I trial for solid tumors as monotherapy in Australia/China and plan
to initiate a combo study with CS1003 (PD-1) thereafter
CS3008 /
Fisogatinib *
(FGFR4)
◼ Conducting a Ph I trial (join global) for HCC as monotherapy in China and
published results (CN part) in CSCO 2020, exploring the registration path for
monotherapy in 3L HCC in China
◼ Conducting a Ph Ib/II trial for HCC as combo with sugemalimab in China and
initiated dose expansion in 3Q2020
NM21-1480
(PD-L1 / 4-1BB /
HSA)
◼ Conducting Ph I trials for solid tumors in US and Taiwan by Numab
Note: in partnership with Blueprint Medicines
HCC = Hepatocellular Carcinoma
28
CStone Pipeline 2.0 Advancement
29
Pipeline 2.0: CStone-driven innovation model for global
FIC/BIC assets
I/O (Combo) & Precision Medicine
TME Multi-specifics ADCCancer
Vaccine(Opportunistic)
CStone-Driven
Innovation
Model
Idea Generation
Project Design1 FIC/BIC
2 Global rightsWork with CRO
on execution
Examples
• 3 multi-specifics,
incl. NM21-1480
• 2 ADCs, incl.
CS5001
Sources of Innovative Ideas
Protein Chemistry PharmacologyProject
Management
Clinical
Pharmacology
DMPK /
Toxicology
Bioinformatics Translation
Med/BiomarkerSABAcademic
Observa-tions
made in the clinic
BD partners
CRO platforms
Archie Tse, MD, PhD
Chief Scientific Officer
Line of sight from Discovery Research to PoC under a single leadership
Note: I/O = immuno-oncology, TME = tumor microenvironment, ADC = antibody-drug conjugate, FIC = first-in-class, BIC = best-in-class, PoC = Proof of Concept
Early Development
Molecular
Diagnostics
• Physician-scientist with 20+ years of
experience in translational oncology
research covering cytotoxics, targeted
agents, and immunotherapies
• Oncology TA Head at Daiichi-Sankyo
responsible for the development and
implementation of overall Oncology TA
strategy
• Oversaw early development of 14 IO
assets of different MOAs and
modalities at MSD
30
■ Combination therapy in one molecule
→expands combo options with SoC and
other ICIs
■ Monovalent 4-1BB binding remains
inactive until PD-L1 engagement
→maximizes safety
■ Ultra-high affinity (pM) to PD-L1
→broadens PD-L1+ tumor types
■ Standard affinity to 4-1BB (nM)
→ensures effective activation
■ HSA extends T1/2 & 100% effector null
→enables convenient dosing & eliminated
undesirable FcgR-mediated activation
■ MW ~70kDa, only half of conventional
mAb
→leads to better tumor penetration &
efficacy
4-1BB
T cell
PD-1
PD-L1
4-1BB
Cancer
T cell
scMATCH3
PD-L1 Negative PD-L1 Positive
Urelumab
NM21-1480
500
1000
Mean relative tumor volume
Time (days)
mean R
TV
(%
of baseline)
0 3 7 10 17 21 2414
Irrelevant IgG (Palivizumab)1
NM21-1186 (0.02 mg/occasion)2
NM21-1186 (0.5 mg/occasion)4
NM21-1186 (0.1 mg/occasion)3
Avelumab7
PDL1 IgG6
PD-L1 IgG + 4-1BB IgG5
Urelumab8
NM21-1480 (PD-L1x4-1BBxHSA) has the potential to be
the BIC molecule as the next generation PD-(L)1 inhibitor
■ Bridge new biology
■ Improve therapeutic index & reduce
unwanted toxic effects
■ Expand combo options & improve
administration convenience
Six key features of NM21-1480
31
LCB71 has the potential to be best-in-class ROR1 ADC
with differentiated technology
Collaboration highlights Differentiated payload design
1
2
▪ CStone to acquire rights for development and commercialization
outside Korea for LCB71, an ROR1 antibody drug conjugate
(“ADC”)
▪ A potential global first-wave / best-in-class drug with monotherapy
and combination applications for multiple solid and hematological
malignancies
▪ ROR1 protein expression is prevalent in a variety of cancers including
leukemia, non-Hodgkin lymphoma, breast, lung, and ovarian cancers
▪ LCB71 leverages proprietary tumor-selective linker (denoted as 1 in
the graph on the right) and tumor-activated pyrrolobenzodiazepine
(“ ”) prodrug toxin (denoted as 2 in the graph on the right) to
address the typical toxicity problem associated with traditional
PBD payloads
▪ It utilizes site-specific conjugation for a precise drug antibody ratio
(“DAR”), enabling homogeneous production and large-scale
manufacturing
Asset Development stage Indications Global value
LCB71
(CStone / LegoChem)
▪ Pre-clinical
▪ Potential best-in-class with differentiated
toxin design and conjugation technology
▪ Multiple solid and
hematological malignancies
VLS-101
(Merck / VelosBio)
▪ Ph I/II
▪ Global first-in-class
▪ TNBC, NSCLC, CLL and
MCL, etc.
• In Nov 2020, Merck acquired VelosBio
$2.75bn for all shares
NBE-002
(BI / NBE Therapeutics)
▪ Entered Ph I in Oct 2020 ▪ TNBC and advanced solid
tumor, etc.
• In Dec 2020, Boehringer Ingelheim
acquired NBE Therapeutics for
~$1.4bn (Euro 1.18bn) for all shares
Recent transactions for ROR1 ADC
Note: TNBC = Triple Negative Breast Cancer, NSCLC = Non-Small Cell Lung Cancer, CLL = Chronic Lymphocytic Leukemia, MCL = Mantle Cell Lymphoma
32
Full-fledged Biopharma Capabilities
33
State-of-the-art manufacturing facility in construction to
be in pilot operation by 2021
Small Molecules Biologics
Compliance with GMP requirements
in China and globally
Planned capacity of biologics plant design:
26,000L for biologics and 1 billion tablets for small molecules
◼ In August 2019, CStone entered into an
agreement with Sungent (state-owned
controlled by Suzhou Industrial Park) to
build manufacturing facility
◼ Commencement of the construction in the
first half of 2020 with pilot operation in 2021
◼ Planned building area of approximately
100,000 sqm
◼ Capabilities: once completed, the complex
will be equipped with integrated capabilities
for R&D, pilot plant, and full commercial
scale manufacturing
◼ Planned capacity: 26,000L for
macromolecule biologics and 1 billion
tablets and capsules for small molecule
drugs
◼ Strategic partnership with Wuxi Biologics on
clinical and commercial stage
manufacturing
Better Quality Control
DriveDownCost
Protection of Key Know-how
Compliance Monitoring
Efficient Planning
Long-term Stable Supply
Value Creation
34
Continuing to bring breakthrough therapies to
cancer patients in China and worldwide
Note:1. For in-licensed assets NDA approval time will depend on our partners’ NDA approval time by US FDA
GIST = Gastrointestinal Stromal Tumor, AML= Acute Myeloid Leukemia, R/R = Relapsed or Refractory, NSCLC = Non-small Cell Lung Cancer, sq = squamous, nsq = non-
squamous, MTC = Medullary Thyroid Cancer, SM = Systemic Mastocytosis, HCC = Hepatocellular Carcinoma, NKTL = Natural KILLER/T Cell Lymphoma, ESCC = Esophageal
Squamous Cell Carcinoma, GC = Gastric Cancer
Self-developed From partners
Expect 4 products
Across 4+ indications1
Expect 6+ products
Across 14+ indications1
Expect 10+ potentially
approved products
Across 20+ indications1
Near-term (2020~2021) Mid-term (2022~2025) Long-term (2026~)
Fisogatinib
HCC
Avapritinib
PDGFRA exon 18 GIST,
SM
Ivosidenib
IDH1 r/r AML, 1L AML
CS3002
CDK4/6
ND21-1480
(PD-L1/4-1BB/HSA)
CS1003 (PD-1)
HCC
Pralsetinib
RET 1L / 2L NSCLC, 1L MTC
Sugemalimab
Stage IV NSCLC (sq & nsq),
Stage III NSCLC, ESCC, GC,
NKTL, CRC (w/ regorafenib)
CS1002
(CTLA-4)
CS3005
A2aR Pralsetinib
RET 2L NSCLC
Sugemalimab
Stage IV NSCLC (sq &
nsq)
CS1003 (PD-1)
HCC
Pralsetinib
RET 1L NSCLC,
RET 2L NSCLC,
1L MTC
SugemalimabStage IV NSCLC (sq &
nsq), Stage III NSCLC,
ESCC, GC, NKTL
Fisogatinib
HCC
Avapritinib
PDGFRA exon 18 GIST,
SM
Ivosidenib
IDH1 r/r AML,
1L AMLAvapritinib
PDGFRA exon 18 GIST
Ivosidenib
IDH1 r/r AMLMolecules from co-development with Pfizer
Molecules from co-development and joint in-licensing with Pfizer
More molecules under co-development or in-licensing agreement with partners
35
Financial summary for 1H 2020
Cash Balance
◼ RMB2,124 million of cash, cash equivalents, and time deposits as of
June 30, 2020 vs. RMB2,726 million as of December 31, 2019
◼ Cash position decreased by RMB602 million mainly due to R&D expenses,
administrative and selling expenses
Sources of
Cash
◼ IPO proceeds: HK$2,394 million (post greenshoe)
◼ Bank borrowing: Available bank loan facility up to RMB200 million for
working capital improvement and the construction of the manufacturing
facility and other facilities
Uses of Cash
◼ R&D expenses (non-IFRS1): RMB470 million
◼ Administrative and selling expenses (non-IFRS1): RMB100 million
Note: 1. Adjusted for share-based compensation
36
Following a fruitful 2020, we expect various thrilling
milestones in 2021
4 products across 4+ indications
5+ NDA filings2 for 3 products
30 trials incl. 17 for registration
Multiple data readout
Revamp of research
organization for Pipeline
2.0 with global
FIC/BIC molecules
Multiple IND filings
Post-PoC
asset nomination for
co-development
with Pfizer
Pilot
operation of
the state-of-the-
art manufacturing
facility
Avapritinib
(KIT/PDGFRA
inhibitor)
Pralsetinib
(RET inhibitor)Sugemalimab1
(PD-L1
antibody)
Ivosidenib
(IDH1 inhibitor)
Commercialization Clinical Development
ResearchBusiness
DevelopmentManufacturing
Note:
1. Pfizer to lead commercialization of sugemalimab in mainland China
2. Expected NDA filings include but not limited to (1) sugemalimab: stage III NSCLC in mainland China; (2) pralsetinib: 1L NSCLC in mainland China; (3) pralsetinib: 1L MTC in
mainland China; (4) pralsetinib: 2L NSCLC in Taiwan; (5) ivosidenib: r/r AML in mainland China
Thank you!