2020 virtual r&d day · 2020. 11. 12. · u.s. status pre-clinical ind phase 1 phase 2 phase 3...
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0Copyright© 2020 Innovent BiologicsConfidential
To develop and commercialize high quality biopharmaceuticals that are affordable to ordinary people
2020 Virtual R&D DayInnovation Drives Excellence
November 10, 2020
1Copyright© 2020 Innovent BiologicsConfidential
Today’s Participants
MICHAEL YU, PhDFounder, Chairman & CEO
YONG-JUN LIU, MD, PhDPresident
Mr. RONNIE EDEExecutive Director,
Chief Financial Officer
Mr. MIN LIU Chief Commercial Officer
JUNJIAN LIU, PhDVP, Drug Discovery
WEI XU, MD, PhDVP, New Drug Biology & Translational Medicine
HUI ZHOU, MD, PhDVP, Medical Science
LEI QIAN, MD, PhDSenior Director, Medical Science
Mr. BLAKE SALISBURYVP, Business Development
Mr. HONG PANSVP, Manufacturing
Engineering Supply Chain
2Copyright© 2020 Innovent BiologicsConfidential
Introduction—Michael Yu1
Agenda
Opening Remarks—Yong-Jun Liu 2
Pipeline Overview and R&D StrategyWei Xu, Junjian Liu, Hui Zhou, Lei Qian
3
Management Discussion on Business UpdateMichael Yu, Yong-Jun Liu, Ronnie Ede, Min Liu,
Hong Pan, Blake Salisbury
4
1
2
3
4
3Copyright© 2020 Innovent BiologicsConfidential
Introduction
Michael Yu, PhDFounder, Chairman & CEO
1
4Copyright© 2020 Innovent BiologicsConfidential
2011-2017
• Successfully listed in HKEX• First Drug TYVYT® was approved by NMPA
2018 2019 2020
• Innovent was established in 2011• Strategic partnership with Eli Lilly in 2015• First manufacturing facility was established
• Launched TYVYT® • TYVYT® was included in China’s NRDL as the
only PD-1 inhibitor• First year revenue for TYVYT® sales was over
RMB 1bn
• Three additional new products were approved by NMPA
• Strategic collaboration with Roche • Licensed out TYVYT®’s ex-China global
rights to Eli Lilly• Included in HSCI and Stock Connect • Named Dr. Liu, a world-class scientist and
industry leader as president
Key Accomplishment since 2011
Four launched biologic drugs
Strong valuable assets in pipeline
High RMB2.5bn+ total sales of TYVYT®1
US$10bn+ market capitalization2
3,300+ talented employees
Note:1. Accumulated total sales from 2019 to 3Q 20202. Market capitalization as of 7 Nov 2020
5Copyright© 2020 Innovent BiologicsConfidential
Major Accomplishment in 2020
Product Globalization
Pipeline Financial
3 New Products Launched Comprehensive Global Partnership
Strengthened Financial Capability
• 1H 2020 revenue: RMB984m
• Cash on hand: US$1.2bn
• Stock Connect: one of the first two 18A biotech listcos included in Stock Connect
• Two follow-on offerings: USD660m, total fund raising from pre-IPO to post-IPO over US$2bn
R&D and Clinical Development• TYVYT®:
- 2 sNDA filed for 1L NSCLC- Met primary endpoint of Ph3 of 1L
HCC (combo), plan to file NDA in 2020
• CD47:- Phase 1b/2: safety proven,
accelerating to pivotal trial
This is a foundation year to continue our new drug development, consolidate our commercialization capability, and start our globalization journey
6Copyright© 2020 Innovent BiologicsConfidential
The fully Integrated Platform Lays Solid Base for Our Long-term Vision
Fully-integrated platform with world-class discovery, development, manufacturing and commercialization capabilities.
Discovery
CMC (Manufacturing & Quality)
ClinicalDevelopment
Commercialization
7Copyright© 2020 Innovent BiologicsConfidential
Innovation and Globalization are Our Key Strategies
Innovation GlobalizationA premier global
biopharmaceutical company
Build on robust pipeline
Focus on unmet patients’ needs
Global leading R&D capabilities and cutting-edge technologies
Collaboration with leading global biopharmaceutical companies
Expand Innovent’s in-house R&D and commercial arms globally
Expand manufacturing capacity globally
By 2030, more commercialized products, including first-in-class products launched globally
Develop
potential global first-in-class
products
Develop and sell Innovent
products globally
8Copyright© 2020 Innovent BiologicsConfidential
Integrate Discovery Engine and Clinical Development in Goal for Potentially First-in-class Products
Innovent Academy
Medical ScienceTranslational Medicine
Product Development • Focuses on clinical development of
identified assets
• Consists of sub-teams in terms of disease area (oncology & non-oncology) and in terms of key indications respectively together with other supporting sub-teams
Technology-enabling • Cutting-edge platform technology to
identify new therapeutic targets e.g. next-generation antibody technology, cell therapy etc
Precision Medicine• Understand MOA to find patients
who respond and who do not
• Use biomarkers to study the MOA of candidate drugs based on clinical data.
Global FICDrug
Biology-driven• Unmet medical needs drive
innovation
• To identify new therapeutic targets via basic research
Innovent has a total of 1,000+ experienced talents in R&D, 23 assets in pipeline under development
9Copyright© 2020 Innovent BiologicsConfidential
Innovation + Globalization: We Have Established Overseas Subsidiaries to Pursue Innovation Globally
Suzhou China
San FranciscoU.S.A
LondonUK
We are enhancing the R&D and BD capability in US and Europe. We expect to further expand the manufacturing capacity and marketing operation for the global market
10Copyright© 2020 Innovent BiologicsConfidential
Recent Deals and Partnership: Accelerate Global R&D and Commercialization
Striving to Be the Partner of Choice
• Total deal value exceeds
US$2.5bn1
• Including upfront payment
of US$256m1
• Access to Roche’s bispecific antibody and Universal CART technologies
• Out-license ex-China global
rights of up to US$ 2.1bn payments and royalties
• Licensed in 3 clinical-stage molecules
• Demonstrated our capability to help global partners bring their innovative therapies into China
Comprehensive global partnership enhances our overall development from R&D to commercialization
Note: 1. Including both 2015 and 2020 strategic deals with Eli Lilly, not including royalties
11Copyright© 2020 Innovent BiologicsConfidential
State-of-the-art Manufacturing Facilities Designed to, Built to, and Operating at International Standards
36,000L
6 x 1,000 L6 x 3,000 L
Total capacity in the future: 60,000 L
M1b Facility
®On 29 December 2018, our manufacturing facilities received cGMP certification from the NMPA for manufacturing TYVYT® (sintilimab)
Facilities were designed to meet FDA, EMA,
PMDA and NMPA standards, and support
the full process from DS to DP. DS, DP and
GMP were successfully audited
Facilities have undergone ordinary course,
comprehensive annual audits to evaluate
compliance with industry cGMP and
quality compliance standards
Manufacturing team has extensive experience
at multi-national bio-pharmaceutical
companies
12Copyright© 2020 Innovent BiologicsConfidential
01
2020• 4 commercialized
products
• More products at late stage development
• Increased GMP manufacturing capacity
• Establish Innovent Academy
02
VISION
2030
• More commercialized products, including first-in-class products launched globally
• To be a premier global biopharmaceutical company
Summary: A Long Term Vision
2025
• Expandedcommercialized productsin China
• Multiple products approved in the international markets
• Commercial supply from overseas manufacturing site
03
13Copyright© 2020 Innovent BiologicsConfidential
Welcome Our New President, Bringing Renowned World-class R&D Expertise and Industry Leadership
Mainly responsible for Innovent’s global R&D, portfolio strategy, business development and international operations;
World renowned scientist in immunology, oncology and translational medicine;
30+ years rich leadership experiences in both academic institutions and top global pharmaceutical companies.
Global Head of Research (2016-2020)
Chief Scientific Officer,Global Head of Research
(2014-2016)
Chief Scientific Officer,Director of the Baylor Immunology
Research Institute (2011-2014)
Vivian Smith Distinguished Chair Professor, Chairman of Department of Immunology
Founding Director of the Center for Cancer Immunology Research (CCIR)
(2002-2011)
Yong-Jun Liu, MD, PhDPresident, Innovent
14Copyright© 2020 Innovent BiologicsConfidential
Opening Remarks
Yong-Jun Liu, MD, PhDPresident
2
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Pipeline Overview and R&D Strategy
Wei Xu, Junjian Liu, Hui Zhou, Lei Qian(in speech order)
3
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Innovent Discovery Strategy and Key Early Stage Pipeline
3.1
Wei Xu, MD, PhDVP, New Drug Biology & Translational Medicine
Junjian Liu, PhDVP, Drug Discovery
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Innovent Discovery Strategy Overview
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Overall Discovery Strategy
Goal
Technology
& Disease
Platform
To develop and launch First-in-class drugs globally in 2025-2030
Technology focus: Antibody (mAb, bi/multi-specific), ADC, Cell therapy
Disease focus: Oncology, Immunology, Metabolic Disorders, Ophthalmology
Unmet medical needs drive innovation
Innovent Academy as powerful discovery engine based on biology and platform technologies
19Copyright© 2020 Innovent BiologicsConfidential
Innovent’s Integrated R&D Platform and Experienced Team
Preclinical Research
Medical Science & Strategy
Clinical Operations
Pharmacovigilance GCP Biostatistics & Info Science
Data Management Clinical Research Regulatory AffairsInternational Operations
Translational medicineDrug discovery
Innovent Academy(n=200+)
Innovent R&D(Led by Dr. Yong-jun Liu, President)
(n=1,000+)
Product Development
(n=750+)
Portfolio Management and Project Management
(n=20)
BD(n=8)
IP(n=20)
20Copyright© 2020 Innovent BiologicsConfidential
Innovent Academy (信达国清院)
Objectives
Innovent’s powerful discovery engine
Driven by both innovation and unmet medical needs
Target to develop and launch FIC product globally
Strategy
Biology-driven technology-enabling (new targets, novel MoA; new drug modalities, other critical technologies)
To address unmet medical needs
People
Renowned industry experts to lead and enhance R&D capability
Including overseas returnees from MNC pharmaceutical companies, employees with rich international industry experience
Platform Technology
Next generation technologies such as protein engineering, antibody engineering, cell therapy, ADC, etc
Utilize Innovent’s established full-integrated platform to facilitate R&D and achieve more synergies throughout the value chain from research to commercialization
民若康国即清
21Copyright© 2020 Innovent BiologicsConfidential
Monoclonal
antibodies
ADC
Innovent’s Key Therapeutic and Technology Focus
Oncology Non-Oncology
Multi-specific
antibodies
Cell Therapy
Ophthalmology• Anti-angiogenesis• Anti-inflammation• Bi-specific molecules
Metabolic diseases • Lipid lowering agents• Glucose lowering agents• Multi-functional molecules
Autoimmunity
• Inflammatory cytokines blockade antibodies
• Tremendous increase in the prevalence of retinal, metabolic and inflammatory/autoimmune diseases worldwide.
• Innovent is taking a leading role in addressing these highly unmet medical needs in China, and worldwide.
• Immunotherapy: great potential to induce durable clinical responses in broad spectrum of cancer patients.
• Targeted therapy: achieve high clinical response rates in biomarker defined cancer patients.
• Innovent selectively focuses on certain next generation technologies with core competency in mAb.
22Copyright© 2020 Innovent BiologicsConfidential
Status
Products Target (s) Therapeutic Area Commercial Rights Pre-clinicalIND
Phase1 Phase 2 Phase 3 NDA LaunchedFiled Accepted
TYVYT® (sintilimab injection) PD-1 Oncology Worldwide
BYVASDA® (bevacizumab injection) VEGF-A Oncology Worldwide
SULINNO® (adalimumab injection) TNF-alpha Autoimmune Worldwide
HALPRYZA® (rituximab injection) CD20 Oncology Worldwide
IBI-375 (Pemigatinib) FGFR1/2/3 Oncology Mainland China, HK, Taiwan, Macau
IBI-306 PCSK9 Metabolic Mainland China, HK, Taiwan
IBI-310 CTLA-4 Oncology Worldwide
IBI-376 (Parsaclisib) PI3Kδ Oncology Mainland China, HK, Taiwan, Macau
IBI-377 (Itacitinib) JAK1 Oncology: GVHD Mainland China, HK, Taiwan, Macau
IBI-362 OXM3 Metabolic Mainland China, HK, Taiwan, Macau
IBI-188 CD47 Oncology Worldwide
IBI-318 PD-1/PD-L1 Oncology Mainland China, HK, Macau
IBI-101 OX40 Oncology Worldwide
IBI-302 VEGF/Complement proteins Ophthalmology Worldwide
IBI-110 LAG-3 Oncology Worldwide
IBI-315 PD-1/HER2 Oncology Worldwide
IBI-326 BCMA-CART Oncology Worldwide
IBI-939 TIGIT Oncology Worldwide
IBI-322 PD-L1/CD47 Oncology Worldwide
IBI-112 IL-23 p19 Autoimmune Worldwide
IBI-323 LAG-3/PD-L1 Oncology Worldwide
IBI-102 GITR Oncology Worldwide
IBI-319 PD-1/4-1BB Oncology Mainland China, HK, Macau
Biologics Small molecules Clinical progress in the U.S.
IND approved: Dec 2016
NDA approved : Sep 30, 2020
IND approved: Jul 2019
IND approved : Apr 2020
NDA approved: Jun 17, 2020
NDA approved : Sep 2, 2020
IND approved: Feb 2018
IND approved : Oct 2020
IND approved: Sep 2017
IND approved: Jun 2018
IND approved: Feb 2019
IND approved: Aug 2018
NDA approved: Dec 24, 2018
IND approved: Nov 2019
IND approved: Nov 2019
IND approved: Nov 2019
IND approved: Jul 2019
IND approved: Apr 2020
IND approved: Sep 2019
IND approved : Oct 2020
IND approved: Jan 2020
IND approved: Jan 2020
Robust Pipeline Across Novel Therapeutics
IND file : Aug 2020
23Copyright© 2020 Innovent BiologicsConfidential
Innovent Key Early Stage Pipeline
CD47/SIRPα Franchise
24Copyright© 2020 Innovent BiologicsConfidential
CD47/SIRPα Franchise Overview
Nat Rev Cancer. 2019, 19(10):568-586
PD1PD-L1
CD47IBI-322
IBI-188
IBI-397
• CD47-SIRPα axis is a critical innate immune checkpoint which bridges innate and adaptive immunity via phagocytosis and antigen presentation. It orchestrates other immune checkpoints to regulate immune surveillance in cancers
• Blocking CD47-SIRPα signal may synergize with T cell checkpoint inhibitors in various tumor types
• CD47-SIRPα franchise is a strong addition to Innovent’s comprehensive IO portfolio IBI-188 (CD47), clinical IBI-322 (PD-L1/CD47), clinical IBI-397 (SIRPα), pre-clinical
25Copyright© 2020 Innovent BiologicsConfidential
IBI-188 (CD47): A Potentially Best-In-Class Anti-CD47 Monoclonal Antibody
188Fab-H188Fab-L
CD47
Hu5F9-G4By Forty-seven
IBI-188By Innovent
Cell. 2010, 142(5):699-713Nat Med. 2015, 21(10): 1209–1215Immunity. 2017, 47(2):363-373.e5
• Fully human antibody
• Unique binding epitope with potent blocking activity of CD47-SIRPα signaling
IBI-188: anti-CD47 mAb
Mechanism of Action Differentiation Status
• Optimized affinity for balanced toxicity and efficacy
• Stronger efficacy than hu5F9 and comparable tolerability in NHPs
• China: Finalizing Phase 1a dosage escalation, initiated 1b/pivotal in 2H20
• US: Completed Phase 1a dosage escalation, initiated Phase 1b in 2H20
26Copyright© 2020 Innovent BiologicsConfidential
Efficacy Comparison between a Benchmark Hu5F9 and IBI-188
Raji xenograft tumors (Lymphoma)
Days post tumor implantation
Tu
mo
r vo
lum
e (
mm
3)
8 11 13 16 20 23 27 30 340
250
500
750
1000
1250
1500
1750 h-IgG
Hu5F9, 0.1mg/kg
IBI188, 0.1mg/kg
********
Robust anti-tumor efficacy of IBI-188 in Raji lymphoma model.
Hu5F9 is an anti-CD47 monoclonal antibody, being developed by Gilead Sciences globally
Raji xenograft tumor model (Lynmphoma)
27Copyright© 2020 Innovent BiologicsConfidential
Combination Therapies of IBI-188 in Different Xenograft Models
0 7 10 14 17 21 24
0
200
400
600
800
Days post tumor implantationT
um
or
vo
lum
e (
mm
3)
hIgG
IBI188
IBI301(Rituximab biosimilar)
IBI188+IBI301
*
*******
Raji Xenograft tumors (Lymphoma)
0 5 10 15 20 25
0
100
200
300
Days post tumor implantation
Tu
mo
r vo
lum
e (
mm
3)
h-IgG
IBI188
IBI305 (VEGF-A)
IBI188+IBI305
MDA-MB-231 xenograft tumors (Breast)*******
*
0 5 10 15 20 25
0
400
800
Days post tumor implantation
Tu
mo
r v
olu
me
(m
m3)
hIgG
IBI188
AZA
IBI188+AZA
MV-4-11 xenograft tumors (AML)
*
****
Superior combinatorial efficacy of IBI-188 with chemotherapy and targeted therapies in AML, lymphoma and breast cancers.
28Copyright© 2020 Innovent BiologicsConfidential
0 2 4 8 9 1 6 2 3 3 0 3 3 4 3 5 6
0
2
4
6
8
1 0
D a y s
4 M 0 0 1
4 M 0 0 2
4 M 0 0 3
4 M 0 0 4
4 M 0 0 5
4 F 0 0 1
4 F 0 0 2
4 F 0 0 3
4 F 0 0 4
4 F 0 0 5
1st
2n d
3th
4th
5thD o s e
IB I1 8 8 -1 0 0 m g /k g
Toxicity of IBI-188 in Cynomolgus Monkeys
•IBI-188 was well tolerated at doses up to 100 mg/kg in GLP multi-dose toxicity and safety studies
•Transient and reversible RBC reduction, attributed to high CD47 expression on mature erythrocytes
• PK profiles typical of IgG with target mediated clearance at low dose range
• Recommended FIH dose warrants significant safety margin based on the preclinical data
0 2 4 8 9 1 6 2 3 3 0 3 3 4 3 5 6
0
2
4
6
8
1 0
D a y s
3 M 0 0 1
3 M 0 0 2
3 M 0 0 3
3 M 0 0 4
3 M 0 0 5
3 F 0 0 1
3 F 0 0 2
3 F 0 0 3
3 F 0 0 4
3 F 0 0 5
1st
2n d
3th
4th
5thD o s e
IB I1 8 8 -2 0 m g /k g
0 2 4 8 9 1 6 2 3 3 0 3 3 4 3 5 6
0
2
4
6
8
1 0
D a y s
2 M 0 0 1
2 M 0 0 2
2 M 0 0 3
2 M 0 0 4
2 M 0 0 5
2 F 0 0 1
2 F 0 0 2
2 F 0 0 3
2 F 0 0 4
2 F 0 0 5
1st
2n d
3th
4th
5thD o s e
IB I1 8 8 -3 m g /k g
0 2 4 8 9 1 6 2 3 3 0 3 3 4 3 5 6
0
2
4
6
8
1 0
V e h ic le
D a y s
1 M 0 0 1
1 M 0 0 2
1 M 0 0 3
1 M 0 0 4
1 M 0 0 5
1 F 0 0 1
1 F 0 0 2
1 F 0 0 3
1 F 0 0 4
1 F 0 0 5
RB
C (
10
12
/L
)
1st
2n d
3th
4th
5thD o s e
29Copyright© 2020 Innovent BiologicsConfidential
IBI-188: Clinical Development Status Summary
Design of Phase1a study in the US/China Clinical development status and planning
1L higher
risk MDS
• Phase 1b/3 ongoing in China & the US
r/r AML
1L unfit
AML
• Phase 1b/2 ongoing in China
• Phase 1b ongoing
- China: Finalizing Phase 1a dosage escalation;- US: Completed Phase 1a dosage escalation;- Well tolerated, Completed all pre-specified seven dosage without any DLT;- Phase 1a study results of IBI-188 has been accepted by SITC 2020
conference as ePOSTER – Nov 11-14, 2020;
Solid
tumors
• Phase 1b study will be initiated to evaluate IBI-188+ sintilimab
30Copyright© 2020 Innovent BiologicsConfidentialCell Res. 2016 Jun;26(6):639-40
Nat Med. 2015, 21(10):1209-15Nature. 2017, 545(7655):495-499
αCD47 αPD-L1 (sdAb x2)
IBI-322 (PD-L1/CD47): A First-in-Class Anti-CD47/PD-L1 Bispecific Antibody
IBI322
Mechanism of Action
Differentiation
Status
• Superior anti-tumor efficacy
- Target both innate and adaptive immunity
- MOA synergy 1: APC activation by CD47 to enhance CTL activity
- MOA synergy 2: PD1+TAM inhibition to boost phagocytosis
• Manageable safety profiles
- Reduced CD47 binding on RBC to mitigate anemia AE
- Decreased RBC phagocytosis due to weak CD47 blockade activity
• Improved DMPK profiles
- Reduced peripheral CD47 mediated sink effect
- Optimized biodistribution and enhanced PD-L1+ tumor uptake
• China: Phase 1 ongoing
• US: IND approved, initiating Phase 1
• Dual blockade of CD47/SIRPα and PD-1/L1 signals can create novel Biological mechanisms and achieve strong synergy in cancer treatment
31Copyright© 2020 Innovent BiologicsConfidential
Red blood cells
H292 tumor cells
Antibody
Anti-CD47
IBI322
Anti-PD-L1
9.20%
86.25%
98.89%
Characterization of IBI-322 Distribution In Vitro and In Vivo
IBI-322 selectively accumulated on PD-L1/CD47 double positive tumor cells both in vitro and in vivo.
Distribution of IBI-322 across red blood cells and tumor cells
• CD47+ PD-L1+ MC38 tumor cells were implanted subcutaneously into the CD47 knocked-in mice.
• 89Zr labeled antibodies were injected at 0.5 mg/kg.
• PET-CT imaging were taken 24 hours after drug administration.
Distribution of IBI-322 in the mouse model
32Copyright© 2020 Innovent BiologicsConfidential
IBI322
αCD47
hCD47+
Tumor cells
SIRPα-mFc
hCD47+/hPDL1+
Tumor cells
SIRPα-mFc
~30 fold
0.001 0.01 0.1 1 10 100 1000
0
2000
4000
6000
8000
10000
12000
hCD47/SIRPα blockingin CD47+ cells
Con (nM)
MFI
CD47
IBI322
hIgG
MF
I (S
IRP
)
hCD47/SIRP blockingin CD47+/PDL1+ cells
Log Con (nM)
FL4
-A M
FI
-4 -2 0 2 40
20000
40000
60000
80000
CD47IBI322
IgG1
PD-L1
MF
I (S
IRP
)
IBI-322 selectively blocked CD47/SIPRα interaction on PD-L1/CD47 double positive cells.
IBI-322 Blockade of CD47/SIRPα Interaction In Vitro
33Copyright© 2020 Innovent BiologicsConfidential
Efficacy of IBI-322 in Humanized Xenograft Tumor Models
Day -5
Raji/PD-L1 cell
Day 0
hPBMC
5 7 9 11 13
Dose Q2dx5
Raji-PD-L1 xenograft model
5 9 12 15 18 22 24 29
0
100
200
300
400
500
600
700
Raji/PD-L1 with h-PBMC in NOD/SCID model
Days post tumor implantation
Tu
mo
r vo
lum
e (
mm
3)
h-IgG (0.2 mg/kg)
PD-L1 (0.1 mg/kg)
CD47 (0.1 mg/kg)
PD-L1+CD47 (0.1+0.1 mg/kg)
IBI322 (0.17 mg/kg)
p=0.0078
1 7 11 14 18 21 25
0
100
200
300
400
500
600
A375 with h-PBMC in NOD/SCID mice
Days post tumor implantation
Tu
mo
r vo
lum
e (
mm
3)
h-IgG
PD-L1 (0.66 mg/kg)
CD47 (0.66 mg/kg)
PD-L1+CD47 (0.66+0.66 mg/kg)
IBI322 (1.1 mg/kg)
p=0.06
Day -5
A375 cell
Day 0
hPBMC
1 3 5 7 9 11
Dose Q2dx6
A375 xenograft model
IBI-322 demonstrated superior efficacy in CD47+PD-L1+ xenograft models reconstituted with human PBMC
34Copyright© 2020 Innovent BiologicsConfidential
Body Weight Changes in Raji-PD-L1 & A375 Models
5 7 9 11 12 13 15 18 22 24 29
-10
0
10
20
30
Body weight change of Raji-PD-L1 model
Days post tumor implantation
Bo
dy
we
igh
t c
ha
ng
e(%
) h-IgG (0.20 mg/kg)
PD-L1 (0.10 mg/kg)
CD47 (0.10mg/kg)
PD-L1+ CD47 (0.1+0.1 mg/kg)
IBI322 (0.17 mg/kg)
1 3 5 7 9 11 14 18 21 25
-10
0
10
20
30
Body weight change of A375 model
Days post tumor implantation
Bo
dy
we
igh
t c
ha
ng
e (
%) h-IgG
PD-L1 (0.66 mg/kg)
CD47 (0.66 mg/kg)
PD-L1+CD47 (0.66+0.66 mg/kg)
IBI322,1.1 mg/kg
No body weight lost when dosed with IBI-322 bispecific Ab, αCD47, αPD-L1 alone or combination in both models.
35Copyright© 2020 Innovent BiologicsConfidential
IBI-322 was better tolerated than hu5F9, with lower RBC toxicities after weekly 10mg/kg dosing in cyno monkeys.
RBC changes in cyno monkeys
day
RB
C (
%)
-5 0 5 10 15 200
20
40
60
80
100
Hu5F9
IBI322
p=0.03
Drug administration
IBI-322 Safety Profile Related to RBC
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IBI-322: Clinical Development Status Summary
Molecule characteristicsClinical development status and planning
Solid tumors
• Phase 1a/Ib: - China: FPI Q2-2020- US: FPI Q4-2020
lymphoma
Myeloid
malignancies
• Phase 1a/1b planned
• Phase 1b planned
• Differentiated clinical development to CD47 mAb,
bispecific of CD47 targeted antibody
Molecule: PD-L1/CD47 bispecific antibody, IgG1 with effector null Fc; Anticipated Mode of Action: • Simultaneously target CD47 and PD-L1 on tumor cells with higher
affinity, to reduce the toxicity of normal tissue• Simultaneously blocking PD-L1/PD-1 and CD47/SIRPa pathway; • Synergistic anti-tumor effect of innate and adaptive immunity
37Copyright© 2020 Innovent BiologicsConfidential
IBI-397 (SIRPα): A Potentially First-in-Class Anti-SIRPα Monoclonal Antibody
IBI-397:
anti-SIRPα mAb
• Highly selective, non-competitive SIRPα antibody that effectively induction of SIRPα degradation on macrophages
• Enhances phagocytosis of tumor cells without affecting T cell activity
Mechanism of Action Differentiation Status
• SIRPα selective, non-competitive inhibitor
• FcγR dependent degradation of SIRPα
• Low risk of RBC/platelets depletion in NHPs
• Preclinical
• Selective SIRPα mAb with differentiated MOAs to achievebetter biodistribution and higher therapeutic index
phagocytosis phagocytosis phagocytosis
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Novel Mechanism of Action of IBI-397 (Alector’s AL008)
IBI-397 (AL008) induces SIRPα degradation on macrophages and phagocytosis of tumor cells.
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RBC toxicity of IBI-397 (Alector’s AL008) in NHPs
IBI-397 (AL008) does not deplete RBC in NHPs.
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Summary of CD47/SIRPα Franchise
Status
Pre-clinicalIND
Phase 1 Phase 2 Phase 3 NDA LaunchedFiled Accepted
Finalizing Phase 1a dosage escalation
China
Initiated Pivotal Phase 1b/2 in r/r AML
Initiated Pivotal Phase 1b/3 in MDS
1H20
2H20E
2H20E
U.S.
Status
Pre-clinicalIND
Phase 1 Phase 2 Phase 3 NDA LaunchedFiled Accepted
Completed Phase 1a dosage escalation
Initiated Phase 1b in MDS
1H20
2H20*Note: In U.S., we will initiate the Phase 1b trial in MDS with plan for a registrational trial thereafter
Data in 2H
Status
Pre-clinicalIND
Phase 1 Phase 2 Phase 3 NDA LaunchedFiled Accepted
Initiated Phase 1 study
China
IND approved, initiating Phase 1 study
1H20
2H20U.S.
IBI-188(anti-CD47)
IBI-397(Anti-SIRPα)
IBI-322(anti-PD-L1/CD47)
Status
Pre-clinicalIND
Phase 1 Phase 2 Phase 3 NDA LaunchedFiled AcceptedChina 1H20
Worldwide
Worldwide
Mainland China, HK, Taiwan, Macau
Target/TA Commercial Rights Trial Region
Innovent has built a comprehensive portfolio in CD47 pathway including mAb, bispecific and anti-SIRPα assets with first-in-class potentials. We are well positioned in CD47 area with more advanced clinical development in China and progressing quickly in US. Phase 1 study shows that IBB-188 has good safety and is well tolerated. Data will be published in this Nov in SITC 2020.
41Copyright© 2020 Innovent BiologicsConfidential
Innovent Key Early Stage Pipeline
IBI-939 (TIGIT)
42Copyright© 2020 Innovent BiologicsConfidential
TIGIT Overview
TIGIT regulates T cell response
Nature Immunology, 2018, 19: 650–652Nature Reviews Cancer, 2012, 12: 671–684
Inhibit stem cell like T cell self-renewal
Dampen NK killing function
Enhance Treg function
IBI-939
TIGIT is a key immune checkpoint with pleiotropic functions in regulating anti-tumor immunity.
43Copyright© 2020 Innovent BiologicsConfidential
IBI-939 (TIGIT): a Highly Potent TIGIT Blocking Antibody
10 -3 10 -2 10 -1 100 101 102 103
0
10000
20000
30000
hTIGIT-CHOS CD155 blocking
Con.(nM)
Med
ian
AP
C-A
IC50
IgG1
0.01188
Tiragolumab
1.459
IBI939
0.3412
10 -2 10 -1 100 101 102 103
0
10000
20000
30000
TIGIT-Jurkat reporter assay
Conc log(nM)
Lu
cif
era
se(L
FM
)
IgG1
Tiragolumab
IBI939
EC50
IgG1
~ 21.26
Tiragolumab
5.265
IBI939
0.8062
Antibody MethodsHuman TIGIT
Cyno TIGIT Rat TIGIT
IBI939SPR
(Biacore)3.48E-10 5.93E-09 1.62E-09
• Strong TIGIT-CD155 ligand blocking to enhance T and Nk cell effector functions
Mechanism of Action Differentiation Status
• Fully human antibody
• High TIGIT binding affinity and strong ligand blocking activity
• China: Phase 1 ongoing
• US: Plan to file IND by end 2020
• TIGIT is a key immune checkpoint with pleiotropic functions in regulating anti-tumor immunity.
• TIGIT is usually co-expressed with PD-1 tumor specific effector cells, and simultaneous blockade of both signals may achieve synergistic anti-tumor activity.
44Copyright© 2020 Innovent BiologicsConfidential
In-vivo Efficacy of IBI-939
Lovo xenograft tumor in PBMC humanized mice model
MC38 syngeneic tumor in hTIGIT trangenic mice model
5 10 15 20 25
0
500
1000
1500
2000
2500
Days post tumor implantation
Tu
mo
r vo
lum
e (
mm
3)
hIgG
αPD-1
TIGIT (BMS) + αPD-1
IBI939 + αPD-1
TIGIT (BMS)
IBI939
0 5 10 15 20 25 30
0
400
800
1200
Days post tumor implantation
Tu
mo
r vo
lum
e (
mm
3)
hIgG
PD-1
TIGIT (BMS) + PD-1
IBI939 + PD-1
TIGIT (BMS)
IBI939
IBI-939 exhibited strong anti-tumor activities as monotherapy or in combination with anti-PD-1 antibody in
different tumor models.
45Copyright© 2020 Innovent BiologicsConfidential
IBI-939: Clinical Development Status Summary
Design of Phase 1 studyClinical development status and planning
Solid tumors• Phase 1a ongoing• US IND prepared
NSCLC Phase Ib PoC study is under study initiation
Preliminary Data Readout and Timeline
Other
squamous cell
carcinomas
Phase Ib/2 planned in 2021
• RP2D mono- and combo with sintilimab H1/2021
Combo:IBI939+sintilimab 200mg Q3W
GI Phase Ib/2 planned in 2021
IBI-939D1
IBI-939D2
IBI-939D5
IBI-939D4
IBI-939D3
ComboD3
ComboD5
ComboD4
46Copyright© 2020 Innovent BiologicsConfidential
Innovent Key Early Stage Pipeline
IBI-112 (IL-23 p19)
47Copyright© 2020 Innovent BiologicsConfidential
IL-23/IL-17 Overview
Nat Med. 2015, 21(7): 719-29Nat Biotechnol. 2016, 34(12): 1218-1219
IL-23 shares p40 subunit with IL-12
• IL-23/IL-17 axis plays an important role in the pathogenesis of psoriasis
• Effective blockade of IL-23 and its receptor has offered great promises in treating psoriasis
• IBI-112, a half-life extended anti-IL-23p19 mAb, has demonstrated best-in-class potential from preclinical studies
48Copyright© 2020 Innovent BiologicsConfidential
Long-term Treatment With 6‒34 Injections In The First Year Are Needed For Psoriasis Patients
https://www.ilumyapro.com/ilumya-dosing-administration/
First 52 weeks of therapy
Half-life extended IL-23 therapeutic antibody might reduce the frequency of injections
49Copyright© 2020 Innovent BiologicsConfidential
IBI-112 (IL-23 p19): a Best-In-Class Anti-IL-23p19 Antibody
IL-17, IL-22
Mechanism of Action
Differentiation
Status
• IBI-112: a humanized anti-IL-23p19 mAb
• Potently blocks the binding of IL-23 to its receptor and thedownstream signaling
• Highly specific binding to the p19 subunit without interferingIL-12 activity
• No direct impact on TH1 pathway
• Half life extension by Fc engineering to reduce dosingfrequency
• Phase 1 ongoing
IBI112
Fc engineered for long acting
• Anit-IL-23p19 antibody has shown significant clinicalbenefit and excellent tolerability in psoriasis patients.
50Copyright© 2020 Innovent BiologicsConfidential
Efficacy and PK Profile of IBI-112 in Animal Models
0 200 400 600 800 1000
0.01
0.1
1
10
100
Time (h)
Co
nc
en
tra
tio
n (
g/m
L) IBI112 1 mg/kg
IBI112 WT Fc 1 mg/kg
Groupt1/2 Cmax AUC Cl
h μg/mL μg/mL*h mL/h*kg
IBI112 299.63 6.45 1756.24 0.51
IBI112 WT Fc 200.08 6.92 1327.58 0.73
Black arrow: intracorneal Munro’s microabscess
IBI-112Control IgG
• IBI-112 demonstrated strong anti-inflammatory effect in vivo, reducing hIL-23-induced mouse ear thickness and inflammation.
• IBI-112 showed outstanding PK profile, with prolonged half-life in cynomolgus monkeys
51Copyright© 2020 Innovent BiologicsConfidential
Clinical development status and planning
IBI-112: Clinical Development Status Summary
Pso
Ph1 study in HV
Planned POC study in Pso in 2021
Planned POC study in IBD in 2021
The Phase 1 study will be completed in 2021.
The POC study in psoriasis will be initiated in 2021.
IBD
FIH
Results of SAD study is planned to be disclosed in 2021/2022.
Design of Phase 1 study
Data readout of IBI-112
IV 100MG
SCREEN Follow up
SC 5mg
SC 25mg
SC 100mg
SC 300mg
SC 600mg
IV 600mg
-28D 0D 21D 112D
52Copyright© 2020 Innovent BiologicsConfidential
Innovent Key Early Stage Pipeline
IBI-302 (VEGF/Complement proteins)
53Copyright© 2020 Innovent BiologicsConfidential
Overview of Immunological and Angiogenic Aspects in AMD Pathogenesis
Nature Reviews Immunololgy. 2013, 13: 438-451
The Angiogenesis Foundation
• Inflammation and angiogenesis are two critical pathological processes in AMD development
54Copyright© 2020 Innovent BiologicsConfidential
IBI-302 (VEGF/Complement proteins): Bispecific Fusion Protein Blocking VEGF/Complement Proteins
Mechanism of Action
Differentiation
Status
• High affinity blocker of VEGF family (VEGF-A, VEGF-B, PlGF etc.) andcomplement (C3b and C4b) proteins that simultaneously inhibitinflammation and angiogenesis pathways
• Phase1b/2 ongoing
• IBI-302 is constructed by domains of human VEGFR1/2 and CR1 on thehuman IgG1 backbone; Fully human sequence with low immunogenicityrisk
• Two-in-one design to achieve dual-signal blockade via single injection
• Dual-targeting the two key AMD pathologicalprocesses (inflammation and angiogenesis) maysynergize to achieve durable responses
IBI-302 structure diagram
55Copyright© 2020 Innovent BiologicsConfidential
IBI-302: Preclinical Efficacy Studies
• IBI-302 at 0.25 mg/eye shows better efficacy than Bevacizumab 1.25 mg/eye in laser induced rhesus CNV model.
• IBI-302 at 4mg/eye shows no significant DLT in Rhesus toxicity study.
56Copyright© 2020 Innovent BiologicsConfidential
IBI-302: Clinical Development Status Summary
Results of SAD study is accepted as Poster presentation in Nov
2020 on annual convention of AAO (American Academy of
Ophthalmology).
Design of SAD studyClinical development status and planning
wAMDPhase 1 in wAMD pts
SAD study completed
wAMD
wAMD/GA
Phse 2a in wAMD pts
MAD study ongoing
POC planned in 2021
Data readout of SAD study
In SAD study, IBI-302 showed good safety profile and promising efficacy
57Copyright© 2020 Innovent BiologicsConfidential
Innovent Key Early Stage Pipeline
IBI-318 (PD-1/PD-L1)IBI-319 (PD-1/4-1BB)
58Copyright© 2020 Innovent BiologicsConfidential
Anti-PDL1 Anti-PD1
Bispecific Antibody Example: IBI-318 (PD-1/PD-L1) Overview
Mechanism of Action
• Targeting multi-signals simultaneously with engineered the antibody to fully activate the immune system
Differentiation
• First PD-1/PD-L1 bispecific Ab that creates new biology• Bridging tumor-T for immune synapse• Directly forming DC-T immune synapse• Disrupting B7.1/PD-L1 cis-interaction on DCs to promote
CD28 co-stimulation on T cells
Status
• Phase Ia dose-escalation completed• Phase Ib/II expansion/pivotal study starting
59Copyright© 2020 Innovent BiologicsConfidential
IBI-318 Creates New Biology by Activating Antigen Presenting Cells
C o n tro l + a P D -1 + a P D -1
+ a P D -L 1
0
2 0 0 0 0
4 0 0 0 0
6 0 0 0 0
8 0 0 0 0
Ju
rk
at
CD
28
-CD
3z
(N
FA
T l
um
ine
sc
en
ce
) **
*****
PD-L1 B7.1 Merge
DC
Mayoux…Xu, Science Translational Medicine, 2020
Cis interaction of PD-L1 and B7.1 on dendritic cells PD-1 and PD-L1 synergize to promote CD28 signaling
Double blockade of PD-1 and PD-L1 is superior to PD-1 monotherapy
60Copyright© 2020 Innovent BiologicsConfidential
IBI-318 Impacts T cell Activation
unpublished
anti-PD-1 +anti-PD-L1 IBI-318
IBI-318 bridges PD-1 PD-L1 interaction during antigen presentation
IBI-318 bridges dendritic cells and T cells to form immunological synapse
IBI-318 Induces B7.1-mediated CD28 Co-stimulation On T cells.
61Copyright© 2020 Innovent BiologicsConfidential
IBI-318 In-vivo Efficacy Valuation
unpublished
IBI318 in H292 model
0 4 8 11 15 18 22 250
200
400
600
800
1000
1200
Tum
or v
olum
e (m
m3 )
Days post tumor implantation
no PBMCs
CTRL h-IgG
aPD-1
aPD-L1
aPD-1 +aPD-L1
IBI318
IBI-318 induces complete-remission in tumor-bearing mice.
Day -5
Human PBMC
Day 0
H292 cells
2 9 12 16
Dose x 4
62Copyright© 2020 Innovent BiologicsConfidential
IBI-318: Clinical Development Status Summary
Clinical Status of IBI-318 Design of Phase 1a study
Solid
tumors
Phase 1b ongoing
r/r NKTCL
CSCC
Phase 1b/2 ongoing
Phase 1b/2 ongoingIBI-318 DL1:0.3 mg, IV Q2W
IBI-318 DL2: 1 mg, IV Q2W
IBI-318 DL3: 3 mg, IV Q2W
IBI-318 DL4: 10 mg, IV Q2W
IBI-318 DL5: 30 mg, IV Q2W
IBI-318 DL6 : 100mg, IV Q2W
IBI-318 DL7 : 300mg, IV Q2W
IBI-318 DL8 : 600mg, IV Q2W
IBI-318 DL9 : 1200mg, IV Q2W
Solid
tumors
Phase 1a completed
RP2D
63Copyright© 2020 Innovent BiologicsConfidential
58 patients have been treated with IBI-318; Preliminary results were disclosed at ASCO 2020;
IBI-318: Clinical Development Status SummaryData Readout for IBI-318
Abstract#:3079
All Grade
(n=15)
Any TRAE 11 (73.3)
Infusion related reaction 3(20%)
Pyrexia 3(20%)
ALT increased 1(6.7%)
Asthenia 1(6.7%)
Conjunctival hyperaemia 1(6.7%)
Constipation 1(6.7%)
Cough 1(6.7%)
Safety:
• No DLT observed from 0.3 mg to 300 mg
• No ≥ G3 TRAE had been observed
• One patient in 300 mg had an immune-related AE (G2 arthritis)
Table: Treatment Related Adverse Events
• Twelve patients had at least one on-study tumor assessment.
• As cut-off date, 3 of 9 pts receiving dose level ≥ 10mg had achieved partial response (1 confirmed, 1 PD after the first PR scan and the other 1 got confirmation on April 2, 2020).
Safety Anti-tumor activity
64Copyright© 2020 Innovent BiologicsConfidential
Bispecific Antibody Example: IBI-319 (PD-1/4-1BB) Overview
Mechanism of Action
• Blocking PD-1:PD-L1/2 signaling to reinvigorate T cells, and co-stimulate 4-1BB for durable effector function and memory formation
• PD-1/4-1BB Bispecific Ab For a prolonged T Cell and NK Immunity
Differentiation
• Reduce potential toxicity by Fc silencing
• Reintroduce cross-linking of 4-1BB via PD-1.
Status
• IND filed
65Copyright© 2020 Innovent BiologicsConfidential
IBI-319 Delivers 4-1BB Agonism Based on PD-1-dependent Cross-linking
unpublished
4-1BB (CD137) is an inducible protein expressed by activated T and NK cells
IBI-319 delivers 4-1BB agonism which is solely dependent on PD-1+ cells
66Copyright© 2020 Innovent BiologicsConfidential
IBI-319 Induced Anti-tumor Activity in Tumor-bearing Mice without Liver Toxicity
Q.W. x 3, i.p.
C57BL/6-hPD-1/hCD137 bearing MC38 tumor
9 13 16 20 23 27
0
500
1000
1500
2000
2500
Days post tumor implantation
Tu
mo
r v
olu
me
(mm
3)
hIgG 10mg/kg
IBI319 0.3mg/kg
IBI319 1mg/kg
IBI319 3mg/kg
IBI319 10mg/kg
n.s.
9 13 16 20 23 27
0
500
1000
1500
2000
2500
Days post tumor implantationT
um
or
vo
lum
e (
mm
3)
hIgG 10mg/kg
IBI308 1mg/kg
IBI308 3mg/kg
IBI319 1mg/kg
IBI319 3mg/kg
aCD137 10mg/kg
n.s.
****
****
(one way ANOVA)
IBI-319
αPD-1+αCD137
IBI-319 induces potent anti-tumor activity IBI-319 is devoid of liver toxicity
IBI-319 appeared to alleviate tissue inflammation observed in aPD1+aCD137 combo treatment.
67Copyright© 2020 Innovent BiologicsConfidential
Summary of Innovent Discovery Strategy and Key Early Stage Pipeline
Established integrated R&D platform
1,000+ talents in R&D and 16 innovative programs at early stage development.
Innovent Academy as the discovery engine which primarily focuses on unmet medical needs and first-in-class products.
Integrated platform combining discovery and product development to help Innovent be better positioned to discover and develop global first-in-class products.
Strategic and selective focus on high-potential therapeutic areas and technologies
Innovent is well positioned in CD47 area with a comprehensive franchise from mAb to bispecific. Quickly progressing clinical trials based on proven safety data.
Innovent has the most robust bispecific pipelines with 6 bispecific product candidates in development. We can expand our core competency in PD-1 to bispecific/multi-specific as next generation IO trend with first-in-class potentials.
Innovent also has non-oncology pipelines for unmet medical need in multiple high-potential diseases areas.
68Copyright© 2020 Innovent BiologicsConfidential
Innovent Clinical Development Strategy and Key Late-stage Pipeline
3.2
69Copyright© 2020 Innovent BiologicsConfidential
Innovent Oncology Pipeline Development and Strategy
Hui Zhou, MD, PhDVP, Medical Science
70Copyright© 2020 Innovent BiologicsConfidential
Innovent Oncology Strategy Overview
71Copyright© 2020 Innovent BiologicsConfidential
Innovent Oncology Development Strategy
BreadthExpanding oncology therapy, from late
stage to early stage cancer
DepthAdvancing
efficacy and prolonging
OS
PrecisionIndividualized
therapy
Adjuvant/Neoadjuvant EGFR
PD-1
Overcomeresistance
EGFRALKIOHER2
Biomarker driven therapy
Delay resistanceTIGITTGF-β
Innovent oncology TA development strategy
Maximize the value of Sintilimab
Accelerate key pipeline development (next generation of I-O, B cell related molecule etc.)
Moving to early stage population and PD-1 resistant patients
Personalized medicine based development
Industry trend for oncology development
72Copyright© 2020 Innovent BiologicsConfidential
Oncology Pipeline Layout: Focusing on Seven Key Tumor Types
肠癌
肝癌
胃癌
食管癌
肺癌
乳腺癌
7 KeyTumor type
03BC272,400 pts
Lymphoma88,200 pts
LC733,000 pts
EC477,900 pts
GC678,100 pts
HCC466,100 pts
CRC376,300 pts
IBI-315 (PD-1/HER2) Sintilimab, IBI-301 (CD20),IBI3376 (PI3K), IBI-188 (CD47)
IBI-305 (VEGF), Sintilimab, IBI-310 (CTLA-4)
Sintilimab, IBI-305 (VEGF), IBI-310 (CTLA-4)
Sintilimab
Sintilimab
Sintilimab, IBI-305 (VEGF)
BC272,400 pts
Lymphoma/AML/MDS
163,000 pts
BC: breast cancerCRC: colorectal cancerHCC: hepatocellular carcinomaGC: gastric cancerEC: esophageal cancerLC: lung cancerAML: acute myelocytic laukemiaMDS: myelodysplastic symdrome
73Copyright© 2020 Innovent BiologicsConfidential
Well Organized Product Development Organization Driving Remarkable Deliveries
2016 2017 2018 20019 2020
r/r cHL
(ORIENT-1)
12M
1L nsqNSCLC
(ORIENT-11)
19.8M
21.4M 1L sqNSCLC
(ORIENT-12)
From FPI to NDA
1L HCC
(ORIENT-32)
19MPDP: product development platform;FPI: first patient inNDA: new drug applicationcHL classic Hodgkin lymphoma
Product Development Platform (PDP)n=750+
Project & Portfolio Management
Preclinical Research
Medical Science & Strategy
Oncology
Medical Sciences &
StrategyNon-
oncology
Clinical Pharmaco-
logy
Clinical Operations (three teams)
Data Manage-
ment & PV
GCP/Quality Assurance
Biostatistics & Info
Science
Regulatory Affairs
International Operations
74Copyright© 2020 Innovent BiologicsConfidential
Sintilimab’s Strategy and Key Pipelines
75Copyright© 2020 Innovent BiologicsConfidential
Sintilimab’s Development Strategy : Backbone Role for Oncology TA
Expand to new combos
Internal pipeline developmentBreakthrough for
key Indications
Achieve the breakthrough and focus on 4 key tumor types
― Lung (ORIENT-3, ORIENT-11, ORIENT-12, ORIENT-31)
― Liver (ORIENT-32)
― Gastric (ORIENT-16)
― Esophagus (ORIENT-15)
Combo with internal pipeline
― CTLA-4 (IBI-310)
― LAG-3 (IBI-110)
― TIGIT (IBI-939)
― FGFR (IBI-375)
― VEGF (IBI-305)
― CD20 (IBI-301)
Sintilimab
Expand to external new combos
― 1L PD-L1+GC (+ramucirumab)
― 3L CRC (+Chidamide)
― Solid Tumors (+Fruquintinib)
― Solid tumor (+Sulfatinib)
76Copyright© 2020 Innovent BiologicsConfidential
ORIENT-11(1L nsqNSCLC) Selected as Oral Presentation in 2020 WCLC Biomarker result presented in 2020 ESMO
ORIENT-11 was one of the three oralpresentations at WCLC 2020 VirtualPresidential Symposium
Clinical result simultaneously published in the Journal of Thoracic Oncology
Biomarker result was presented asmini-oral at ESMO 2020
77Copyright© 2020 Innovent BiologicsConfidential
Both PFS and OS Significant Improvement Achieved in ORIENT-11
ORIENT-11[1] KEYNOTE-189[2] NCT03663205[3] NCT03134872[4]
Product Sintilimab Pembrolizumab Tislelizumab Camrelizumab
Design Double-blind Double-blind Open label Open label
PFS (by IRRC)
Median (95%CI), months
8.9 (7.1, 11.3) vs 5.0 (4.8, 6.2)
8.8 (7.6, 9.2) vs 4.9 (4.7, 5.5)
9.7 (7.7, 11.5) vs 7.6 (5.6, 8.0)
11.3 (9.5, NR) vs 8.3 (6.0, 9.7)
HR (95%CI) 0.48 (0.36, 0.64) 0.52 (0.43, 0.64) 0.65 (0.46, 0.90) 0.61 (0.46, 0.80)
P <0.00001 <0.001 0.0044 0.0002
OS
Median(95%CI), months
NR vs NR NR vs 11.3 (8.7, 15.1)
Not reported NR (17.1, NR) vs 20.9 (14.2, NR)
HR (95%CI) 0.61 (0.40, 0.93) 0.49 (0.38, 0.64) 0.72 (0.52, 1.01)
P 0.01921 <0.001 0.0272
Number at Risk
Sint+Chemo 266 231 202 143 63 25 3 3 0
PL+Chemo 131 106 77 42 19 4 1 0 0
Events HR (95% CI) P
Sint+chemo 42.1% 0.482(0.362, 0.643)
<0.00001PL+chemo 65.6%
Pro
gres
sio
n-f
ree
surv
ival
Number at Risk
Sint+Chemo 266 262 248 206 134 72 18 3 0
PL+Chemo 131 128 113 92 61 33 8 1 0
Events 6-mo OS rate HR (95% CI) P
Sint+chemo 19.2% 89.6% 0.609(0.400,0.926)
0.01921PL+chemo 29.8% 80.4%
PFS (by IRRC)
OS
[1] Zhang L, et al. WCLC 2020[2] Gandhi L, et al. NEJM 2018. DOI: 10.1056/NEJMoa1801005
[3] Lu S, et al. ESMO 2020[4] Zhou CC, et al. WCLC 2019
Sintilimab in combination with chemo demonstrated larger decrease of progression and death hazard as 1L therapy for non-squamous NSCLC.
78Copyright© 2020 Innovent BiologicsConfidential
ORIENT-12 (1L sqNSCLC): a Globally First Phase 3 Study to Show PFS Benefit of PD-1 + GP as 1L Therapy for sqNSCLC
ORIENT-12[1] KEYNOTE-407 (N=559)[2] BGB-A317-307 (N=360)[3]
Product Sintilimab Pembrolizumab Tislelizumab
Study design Double-blind; Sintilimab + GP vs placebo + GP
Double-blind; Pembro + CP or CnP vs placebo + CP or CnP
Open-label; Tislelizumab +CP vs TCnP vs CP
PFS (IRRC)HR (95%CI)
0.536 (0.422, 0.681) 0.56 (0.45-0.70) 0.524 (0.370-0.742); 0.478 (0.336-.679)
P <0.00001 0.001 0.0001
OS HR (95%CI) 0.567 (0.353, 0.909) 0.64 (0.49, 0.85) Not reported
P 0.01701 <0.001
[1] Zhou C, et al. ESMO 2020[2] Paz-Ares L, et al. NEJM 2018. DOI: 10.1056/NEJMoa1810865
[3] Jie W, et al. ASCO 2020
Globally, ORIENT-12 is the first randomized Ph3 study to show benefit of anti-PD-1 plus gemcitabine and platinum as 1L therapy for squamous NSCLC.
PFS (IRRC) PFS (INV) Overall Survival
79Copyright© 2020 Innovent BiologicsConfidential
ORIENT-32 (1L HCC): Global First PD-1 Combo Study Has Met Primary Endpoints
N=571
ACCEPTED for Proffered Paper presentationat the ESMO Asia Virtual Congress 2020
ORIENT-32 Study Met Its Primary EndpointsPress Conference on Sep 28,2020
80Copyright© 2020 Innovent BiologicsConfidential
Sintilimab Combo With External Molecule (ramucirumab, anti-VEGFR)
Ramucirumab+anti-PD-1 Ab POC data in PD-L1+ GC
Line Targets Trials PD-L1 mDoRmPFS
(95%CI)
mOS
(95%CI)
1st
lineP+V
JVDF
Cohort A2CPS≥1 NR
8.6
months
(1.5-13.5)
17.3
months
(8.6-NE)
≥3rd
lineP+V
JVDF
Cohort A, BCPS≥1
12.1
months
(6.7-17.5)
4.6
months
(2.3-8.5)
12.6
months
(4.7-20.3)
ORIENT-106:ESMO2020 poster 1498TIPSintilimab+Ramucirumab in 1st line treatment of G/GEJ AC
Study design
81Copyright© 2020 Innovent BiologicsConfidential
Sintilimab-based Internal Pipeline Development in Combination
CTLA-4
Sintilimab
LAG-3 FGFR
TIGIT
IBI-310 (CTLA4)
• Phase III study is ongoing
― Melanoma adjuvant
― Another two pivotal studies for new
indications are being planned
IBI-110 (Lag3)
• Phase Ib study is ongoing
― Combo dose escalation
― Several indications may be planned
to be further developed
IBI-939 (TIGIT)
• Phase Ib study is ongoing
― Combo dose escalation
― Two indications will be focused to be
further developed
IBI-375 (FGFR1/2/3)
/Pemigatinib
• CCA
• UC
82Copyright© 2020 Innovent BiologicsConfidential
Innovent Other Key Oncology Late Stage Pipeline
83Copyright© 2020 Innovent BiologicsConfidential
IBI-310 (CTLA-4) Development Overview: Safety and Clinical Development Status
Part A (Ia): IBI-310N=10
Part B+C (Ib): IBI-310 + sintilimab
N=17
DLT No DLT No DLT
AE ≥ grade 3 No AEs of ≥ grade 3One AE of ≥ grade 3: AST
increased
Melanoma subtypesPart A (Ia): IBI-310
N=10
Part B+C (Ib):IBI-310 + sintilimab
N=17
Mucosal 6 (60%) 5 (31.3%)
Acral 3 (30%) 2 (12.5%)
Non-chronic sun damaged
1 (10%) 9 (56.3%)
chronic sun damaged 0 1 (5.9%)
Disclosed at ASCO 2020 Abstract
IBI-310 has shown good safety profile in Phase 1a/b studies and progressed into registration trials for multiple indications.
Melanoma
HCC
Cervical
Phase 3 trial in adjuvant setting
Phase 2 trial in 2nd line
Phase 3 trial in 1st line
Phase 2 trial in 2nd line
Phase 1a/b Safety Data (N=27) Clinical program of IBI-310 + sintilimab in Phase 2/3
84Copyright© 2020 Innovent BiologicsConfidential
IBI-375 (FGFR1/2/3) Exhibits a Best-in-Class Profile with Excellent Potency for FGFR 1, 2, and 3
Cellular potency
Desired target activity
Off-target activity
1. Guagnano et al (2011) J. Med. Chem; 2. Babina & Turner (2017), Nature Reviews Cancer; 3. Hall et al (2016) PLoS ONE 11(9); 4. Lorenzi et al (2017) Molecular Cancer Therapeutics
Enzyme Inhibitory Activity of IBI375
Biomarkers for FGFR inhibitor sensitivity: FGFR Translocations > Activating mutations > Gene amplifications
IBI-375
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IBI-375 Development Program Overview
PFS
OS
Fight202 study: IBI-375 in Patients with Previously Treated Cholangiocarcinoma outside China
• Adults with locally advanced or metastatic cholangiocarcinoma
• FGFR2 fusion• Progression after ≥1 prior therapy• ECOG PS ≤1• Adequate hepatic/renal function
Oral IBI375,13.5 mg QD (2 weeks on, 1 week off, until disease progression or unacceptable toxicity )
Primary Endpoint: ORR by IRRC Secondary endpoint: PFS, DOR, OS
Study design
Clinical development strategy
• 1L Cholangiocarcinoma phase 3 study
• 1L UC: combo with PD-1
• CCA: combo with PD-1
• NSCLC: combo with PD-1
• Solid tumors with FGFR1/2/3 alterations
Registration study for 1st indication in China:Bridging study in 2L Cholangiocarcinoma patients
Fast progressing IBI-375 with pivotal Phase 2 ongoing in China and several more indication development in plan.
Abou-Alfa GK, et al. Lancet Oncol. 2020 May;21(5):671-684.
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IBI-376 (PI3Kδ) Is a Highly Selective, Potent and Differentiated PI3Kδ Inhibitor Designed to Reduce Hepatotoxicity
p85
• Survival• Proliferation• Growth• Migration• Metabolism
AKTLyn
CD19
SYK
BCAP
lgα lgβ
p110δ
BCR
mTOR
BAD
PI3Kδ
Antigen
GSK3β
FOXO
p27
BAD = Bcl-2-associated death promoter; BCAP = B-cell adaptor for phosphoinositide 3-kinase; FOXO = Forkhead box protein O; GSK-3b = glycogen synthase kinase 3 beta; Ig, immunoglobulin; LYN = tyrosine-protein kinase Lyn; mTOR = mechanistic target of rapamycin; SYK = spleen tyrosine kinase.
IBI-3762 Copanlisib3 Idelalisib4 Umbralisib4
PI3Kδ enzyme potency
(IC50, nM)
1 0.7 2.5 22
Fold selectivity
PI3Kα > 20,000 1 > 300 > 10,000
PI3Kβ > 20,000 5 > 200 >50
PI3Kγ 19,000 10 > 35 > 48
Enzyme Inhibitory Activity of IBI-376 Against Different Members of the Human Class I PI3K Family
• IBI-376 is a novel, potent, and highly specific PI3Kδ inhibitor1 with a differentiated profile for potency (whole blood IC50=10 nM, IC90=77 nM) and dose (<50 mg total daily dose)1
IC50, half-maximal inhibitory concentration; IC90, 90% inhibitory concentration.1. Phillips TJ, et al. ASH 2016. Poster 4195; 2. Shin N, et al. AACR 2015. Poster 2671; 3. Liu N, et al. Mol Cancer Ther. 2013;12:2319-2330; 4. Lanutti BJ, et al. Blood. 2011;117:591–594; 5. Burris HA, et al. ASCO 2016; Poster 7512.
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IBI-376 Development Program Overview
IBI-376 demonstrated a high rate of rapid and durable response in r/r FL
• PIVOTAL trial of IBI376 in R/R FL, MZL in US has completed patients enrollment
• PIVOTAL trial of IBI376 treating relapsed/refractory FL/MZL in China are on going
IBI-376 shows the BIC potential in multiple B cell malignancies; pivotal Phase 2 trial is ongoing in China.
Phase 2 Study Evaluating the Efficacy and Safety of Parsaclisib in Patients with Relapsed or Refractory Follicular Lymphoma (ASH 2020)
IBI-376 had an acceptable safety profile and was generally well tolerated.
Among the 106 patients evaluable for safety in patients
with relapsed or refractory follicular lymphoma:
─ The most common treatment-emergent adverse events (TEAE) were diarrhea (27.4% of patients), nausea (22.6%), cough (18.9%), and fatigue (15.1%);
─ The most common TEAEs grade ≥3 were diarrhea (9.4% of patients), neutropenia (6.6%), and colitis (3.8%).
─ New or worsening grade ≥3 laboratory test values of clinical interest included increase in alanine/aspartate amino transferase (0.9%/0% of patients);
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Status
Products Target (s) Therapeutic Area Commercial Rights Pre-clinicalIND
Phase1 Phase 2 Phase 3 NDA LaunchedFiled Accepted
TYVYT® (sintilimab injection) PD-1 Oncology Worldwide
BYVASDA® (bevacizumab injection) VEGF-A Oncology Worldwide
HALPRYZA® (rituximab injection) CD20 Oncology Worldwide
IBI-375 (Pemigatinib) FGFR1/2/3 Oncology Mainland China, HK, Taiwan, Macau
IBI-310 CTLA-4 Oncology Worldwide
IBI-376 (Parsaclisib) PI3Kδ Oncology Mainland China, HK, Taiwan, Macau
IBI-377 (Itacitinib) JAK1 Oncology: GVHD Mainland China, HK, Taiwan, Macau
IBI-188 CD47 Oncology Worldwide
IBI-318 PD-1/PD-L1 Oncology Mainland China, HK, Macau
IBI-101 OX40 Oncology Worldwide
IBI-110 LAG-3 Oncology Worldwide
IBI-315 PD-1/HER2 Oncology Worldwide
IBI-326 BCMA-CART Oncology Worldwide
IBI-939 TIGIT Oncology Worldwide
IBI-322 PD-L1/CD47 Oncology Worldwide
IBI-323 LAG-3/PD-L1 Oncology Worldwide
IBI-102 GITR Oncology Worldwide
IBI-319 PD-1/4-1BB Oncology Mainland China, HK, Macau
Biologics Small molecules Clinical progress in the U.S.
NDA approved : Oct 9, 2020
IND approved: Jul 2019
NDA approved: Jun 19, 2020
IND approved: Sep 2017
IND approved : Oct 2020
IND approved: Jun 2018
IND approved: Feb 2019
IND approved: Aug 2018
NDA approved: Dec 24, 2018
IND approved: Nov 2019
IND approved: Nov 2019
IND approved: Nov 2019
IND approved: Jul 2019
IND approved: Sep 2019
IND approved : Oct 2020
IND approved: Jan 2020
IND approved: Jan 2020
Summary: Innovent Robust Oncology Pipeline Across Novel Therapeutics
IND file : Aug 2020
3 assets approved, 3 assets in registrational studies, 10 assets in Phase 1 or 2 clinical studies
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Clinical Data Readout Update Plan for Oncology Pipeline
Meeting Product StudiesProjected release date
SITC IBI-188 Phase 1a trial Nov 10-Nov 14
ESMO Asia Sintilimab/IBI-305 Phase 3 study in 1L HCC Nov 20-Nov 22
ESMO Asia Sintilimab Preliminary results of sintilimab in combo with anlotinib in 1L HCC Nov 20-Nov 22
ESMO Asia Sintilimab Preliminary results in neoadjunvant setting of esophageal cancer Nov 20-Nov 22
ESMO Asia Sintilimab Neoadjuvant sintilimab with TiP in locally advanced gastric cancer Nov 20-Nov 22
ESMO Asia Sintilimab Sintilimab+CIK+chemo in lung cancer Nov 20-Nov 22
ESMO Asia Sintilimab Sintilimab+Docetaxel in lung cancer Nov 20-Nov 22
ESMO Asia Sintilimab Neoadjuvant sintilimab+chemo in resectable ESCC Nov 20-Nov 22
ASH Sintilimab Hematologic malignancies Dec 5-Dec 8
ASH IBI376 (Parsaclisib)Phase 2 study evaluating the efficacy and safety of parsaclisib in patients with relapsed or refractory follicular lymphoma (ASH 2020)
Dec 5-Dec 8
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Non-oncology Pipeline Development and Strategy
Lei Qian, MD, PhD Senior Director, Medical Science
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Innovent Non-oncology Pipeline Overview
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DIA/Obesity/NASH CV
Diabetes1. 1st line 2. Oral failure 3. Add-on insulin
IBI-362(GLP-1/GCGR)
1. Obesity 2. Overweight with
complications
IBI-362(GLP-1/GCGR)
NASH IBI-362(GLP-1/GCGR)
OphthalmologyAuto-immune
1. AS 2. RA 3. Pso4. Uveitis
IBI-303(TNF-α)
Hypercholesterolemia1. HoFH2. HeFH3. Non-FH
IBI-306(PCSK9)
1. W-AMD 2. DME 3. GA
IBI-302(VEGF/Compl
ement )
1. Pso2. Psoriatic Arthritis 3. UC 4. CD
IBI-112(IL-23 p19)
Innovent Non-Oncology Pipeline Overview
Innovent non-oncology has covered most of the attractive disease areas
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Development Status of Our Non-oncology Pipeline
Target Therapeutic
Area
Current Status
Pre-clinic IND IND
Approval Ph1 Ph2 Ph3 NDA launched
IBI-303 TNF-α Autoimmue
IBI-306 PCSK9 Metabolic Disease
IBI-302 VEGF/Complement Eye disease
IBI-362 GLP-1/GCGR Metabolic Disease
IBI-112 IL-23 p19 Auto Immune
Innovent is determined to build a robust pipeline for unmet medical needs in the non-oncology areas
IBI-302,IBI-112 are discussed in Section 2. IBI-306 and IBI-362 are discussed in this section
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Innovent Key Non-oncology Late Stage Pipeline
IBI-306 (PCSK9)
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IBI-306 (PCSK9) Overview: A Potentially Long-acting PCSK9 Inhibitor
Clinical Status
Mechanism of Action
• IBI306 is in Phase 3 clinical trials
Differentiation
• Based on the clinical date accumulated, we believe IBI306 demonstrated the potential of being development as a long-acting PCSK9 inhibitor, with dosing internal 6 weeks
• Development status of IBI306 still is ahead of other domestic PCSK9 mAb
European Cardiology Review 2014;9(2):65–70
• As a PCSK9 inhibitor, IBI306 decrease the LDL-C level by decreasing the level of PCSK9 and increasing LDL-R expression on cellular surface of hepatocytes.
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SAD/MAD Study Design for IBI-306
Single Ascending Dose (SAD) Study in Chinese health subjects
Multiple Ascending Dose (MAD) Study in Chinese subjects with hypercholesterolemia
Early stage clinical studies were conduct in HV and Non-FH respectively, and with intention to explore the long acting potential.
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SAD/MAD: Good Safety Profile and Dose-dependent LDL-C Reduction
Phase 1: Percentage Change from Baseline in LDL-C Levels
Phase 2: Percentage Change from Baseline in LDL-C Levels
The point estimate and 95% confidence interval for the difference in percent reduction from baseline in LDL-C for each dose group compared with placebo are as follows:
• 75 mg Q2W: -58.91% (-76.54%, -41.28%)
• 140 mg Q2W: -51.89% (-70.09%, -33.68%)
• 300 mg Q4W: -57.73% (-72.89%, -42.57%)
• 420 mg Q4W: -69.85% (-84.43%, -55.26%)
• 450 mg Q6W: -59.95% (-78.81%, -41.10%)
• 600 mg Q6W: -54.11% (-73.78%, -34.44%)
The safety profile of IBI-306 in MAD is consistent with that in SAD
• Incidence of TEAE between IBI-306 and placebo group is similar.
• No SAE is reported.
Data of SAD and MAD was disclosed in ESC, Aug 2020
In SAD/MAD studies, IBI-306 demonstrated good efficacy/ safety profile, and the potential to be developed as long-acting PCSK9 inhibitor.
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c
IBI-306Innovent
Imported PCSK9iAmgen, Sanofi
Other DomesticPCSK9i
Status Ph3 On market Ph1/Ph2/Ph3
IndicationsHoFHHeFH
Non-HF
HoFHHeFH
Non-HF
HoFHMixed Dyslipidema
Duration Q4W or Q6W Q2W or Q4W Q2W or Q4W
Efficacy50-70% LDL-C
decreased50-70% LDL-C
decreasedNot disclosed
Safety Comparable with each other Not disclosed
Patient Size in China
1200 300-500 600-900
IBI-306: A Potentially Long-acting anti-PCSK9 Monoclonal Antibody
Compared with other PCSK9 inhibitors, IBI-306 has long-acting potential, good efficacy comparable to imported brands, and fastest clinical progress among domestic PCSK9 in China.
Clinical development status
HoFH Phase 2b/3 ongoing
HeFH
Non-HF
Phase3 ongoing
Phase3 ongoing
• Patients enrollment of pivotal studies of IBI306 will be completed in 2021
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Innovent Key Non-oncology Late Stage Pipeline
IBI-362 (GLP-1/GCGR)
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IBI-362 (GLP-1/GCGR) Overview: A Weekly GLP-1/GCGR Dual Agonist
• Phase 2a for Obesity Study:Patients enrollment was completed already
• Phase 2a for Diabetes Study: Patients enrollment expects to be completed in 2020
Clinical Development Status
Differentiation
• The preliminary results of IBI-362 in patients with obesity/overweight was very impressive, demonstrated good tolerability/safety profile and very promising efficacious effect.
Mechanism of Action
• Comparing with activating GLP-1 R only, IBI-362 may activate GLP-1/Glucagon receptor simultaneously as an weekly OXM analog.
• The ratio of activation between GLP-1 and glucagon receptor by IBI362 was optimized compared with that of nature OXM.
• Dual activation of GLP-1/GCGR may bring additional CV benefit like 1) More weight loss 2) Lipid spectrum improvement 3) Decreasing Liver fat.
补充作用机理
IBI362
IBI362 is a GLP-1R and GCGR dual co-agonist.
GLP-1 Effects GCGR Effects
IBI362 is a GLP-1 and GCGR dual agonist. OXM analogs increase insulin secretion. With
chronic administration, OXM will result in significant weight loss and improved insulin
sensitivities. OXM analogs also possess the potential to increase energy expenditure and
improve lipid profiles.
Adapted from GASTROENTEROLOGY.132:2131-2157
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InsulinSecreta-gogues
Met TZDSGLT-2
inhibitorsAGI
DPP-IVInhibitors
Insulin GLP-1 RAOXM3
GLP-1/GCG R dual agonist
MOA
IncreaseInsulin
secretion
Improve insulin resistance
(liver)
Improve insulin
resistance(Peripheral
tissue)
increase glucose
excretion,
Decreaseglucose
absorption
Increase endogenous
level ofGLP-1
Supplement exogenous
insulin
Supplement exogenous
GLP-1
Supplement exogenousOXY
Efficacy(A1c decrease)
++ ++ + + + + +++ ++/+++ +++
Hypoglycemia risk ++ +/- +/-+/-
+/-+/-
++++/- +/-
Weight +/-
+/-
CV benefit — ++ — +++/-
+/-— ++ ++ ??
Dosing Daily Daily Daily Daily Bid/Tid DailyDaily
(Tid-Qd)Daily to Weekly Weekly
Administration oral oral oral oral oral oral IH IH IH
Glucose plusNASH/Obesity/
PCOS/LIPIDX √ X √ X X X √ √
Overview of Marketed Anti-hyperglycemia Agents
OXM3 as a weekly GLP-1/GCGR dual agonist, may offer better options compared with other classic anti-hyperglycemia agents
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Physiology of GLP-1,Glucagon and GIP Activation
J Intern Med.2018,284(6)581-602.
GLP-1R Activation
─ Enhance insulin secretion and inhibit glucagon secretion.
─ Slow gastric emptying, increase satiety and reduce weight gain.
─ Anti-inflammation
─ CV benefit
GCGR Activation
─ Enhance insulin secretion
─ Increase gluconeogenesis
─ Increase energy expenditure
─ Increase the Level of FGF21
GIPR Activation
─ Increase insulin synthesis and secretion
─ Protect Beta cell
─ Increase Lipogenesis
OXM3, may bring more weight loss and more metabolic improvement on lipid, liver enzyme etc. compared with other GLP-1 RAs and other dual agonists
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Summary: Innovent Non-oncology Pipeline Development
Upcoming milestone/catalyst by end 2020 or 2021Five featured non-oncology assets with differentiated position
Build non-oncology into another pillar of Innovent
IBI-303 (Humira Biosimilar)
• Launched as third to market Humira biosimilar
IBI-306 (PCSK9)
• Long-acting potential, good efficacy comparableto imported brands, and fastest clinical progress inPhase 3 among domestic PCSK9 in China.
IBI-362 (GLP-1/GCGR)
IBI-112 (IL-23)
IBI-302 (VEGF/Compliment
protein)
• A potentially FIC weekly GLP-1/GCGR dual agonist.Broad potential indications incl. obesity, diabetesand NASH
• A potentially Phase 1 BIC IL-23 with long-actingfeature to potentially bring better patientcompliance
• A FIC bispecific protein in Phase 1b/2 withpreliminary good safety/efficacy data. Potentialsuperiority to exiting VEGF therapy.
• Already launched.• Acquire new indication through extension as Humira biosimilar.
• Complete all phase 3 trials patient enrollment in 2021.
• The Phase 2a obesity and diabetes study results may be disclosed in 2021.
• The POC study will be initiated in 2021 in obesity and diabetes indications.
• Plan to file IND submission on NASH in 2020
• The Phase 1 study will be completed in 2021.• The POC study in psoriasis will be initiated in 2021.
• MAD study of IBI 302 will be completed in 2021;
• POC study of IBI 302 will be initiated in wAMD and other indications.
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Summary: Robust R&D Platforms and Product Candidates
IBI-308 (PD-1)
IBI-301 (CD20)
IBI-305 (VEGF-A)
IBI-310 (CTLA-4)
IBI-102 (GITR)
IBI-188 (CD47)
IBI-101 (OX40)
IBI-110 (LAG-3)
IBI-939 (TIGIT)
IBI-375 (FGFR1/2/3)
IBI-376 (PI3Kδ)
IBI-377 (JAK1)
IBI-326 (fully human BCMA CAR-T)
Roche partnership
Oncology Pipeline
IBI-318 (PD-1/ PD-L1)
IBI-315(PD-1/HER2)
IBI-322 (PD-L1/ CD47)
IBI-323 (LAG-3/PD-L1)
IBI-319 (PD-1/4-1BB)
Roche partnership
105Copyright© 2020 Innovent BiologicsConfidential
Summary: Robust R&D Platforms and Product Candidates (Cont’d)
Non-oncology Pipeline
IBI-362 (GLP1/GCCR)IBI-302
(VEGF/Complement)
IBI-306 (PCSK9)IBI-303 (TNF-α)
IBI-112 (IL-23 p19)
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Pipeline Overview and R&D Strategy
Q&A
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Management Discussion on Business Update
Michael Yu, Yong Jun Liu, Ronnie Ede, Min Liu,Hong Pan, Blake Salisbury
4
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