2020 virtual r&d day - innovent bio€¦ · copyright© 2020 innovent biologics 22 confidential...

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


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


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


Introduction

Michael Yu, PhDFounder, Chairman & CEO

1


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


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


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


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


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


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


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


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


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


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


Opening Remarks

Yong-Jun Liu, MD, PhDPresident

2


Pipeline Overview and R&D Strategy

Wei Xu, Junjian Liu, Hui Zhou, Lei Qian(in speech order)

3


Innovent Discovery Strategy and Key Early Stage Pipeline

3.1

Wei Xu, MD, PhDVP, New Drug Biology & Translational Medicine

Junjian Liu, PhDVP, Drug Discovery


Innovent Discovery Strategy Overview


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


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)


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


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.


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: Aug 2018

NDA approved: Dec 24, 2018

IND approved: Nov 2019




IND approved: Apr 2020



IND approved: Jan 2020


Robust Pipeline Across Novel Therapeutics

IND file : Aug 2020


Innovent Key Early Stage Pipeline

CD47/SIRPα Franchise


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


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


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)


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


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


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.


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


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


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


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


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


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


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


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


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


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.


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



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


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


• 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


Novel Mechanism of Action of IBI-397 (Alector’s AL008)

IBI-397 (AL008) induces SIRPα degradation on macrophages and phagocytosis of tumor cells.


RBC toxicity of IBI-397 (Alector’s AL008) in NHPs

IBI-397 (AL008) does not deplete RBC in NHPs.


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


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


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.



IBI-939 (TIGIT)


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.


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


• 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.


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


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


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.



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



IBI-112 (IL-23 p19)


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


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


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.


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


Clinical development status and planning


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



IBI-302 (VEGF/Complement proteins)


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


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


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.



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



IBI-318 (PD-1/PD-L1)IBI-319 (PD-1/4-1BB)


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


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


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.


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 )


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



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 DL6 : 100mg, IV Q2W



IBI-318 DL9 : 1200mg, IV Q2W

Solid

tumors

Phase 1a completed

RP2D


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


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


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


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


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.


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.


Innovent Clinical Development Strategy and Key Late-stage Pipeline

3.2


Innovent Oncology Pipeline Development and Strategy

Hui Zhou, MD, PhDVP, Medical Science


Innovent Oncology Strategy Overview


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


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


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


Sintilimab’s Strategy and Key Pipelines


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)


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


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.


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


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


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


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


Innovent Other Key Oncology Late Stage Pipeline


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


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


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.


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.


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);


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


NDA approved: Jun 19, 2020



IND approved: Jun 2018


IND approved: Aug 2018

NDA approved: Dec 24, 2018









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


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


Non-oncology Pipeline Development and Strategy

Lei Qian, MD, PhD Senior Director, Medical Science


Innovent Non-oncology Pipeline Overview


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


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


Innovent Key Non-oncology Late Stage Pipeline

IBI-306 (PCSK9)


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.


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.


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.


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


Innovent Key Non-oncology Late Stage Pipeline

IBI-362 (GLP-1/GCGR)


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


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


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


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.


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


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)


Pipeline Overview and R&D Strategy

Q&A


Management Discussion on Business Update

Michael Yu, Yong Jun Liu, Ronnie Ede, Min Liu,Hong Pan, Blake Salisbury

4

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