Company Overview · Dorzagliatin Mono-therapy Trial for Drug Naïve T2D Patients (463 Patients) HMM0302: 24-week completed February 16, 2020 Dorzagliatin Metformin Add-on Therapy

Company Presentation 2020Q2

Hua Medicine华领医药

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Company Overview

Mission, Vision and Strategy

4

Copyright © Hua Medicine 2020

Become a global diabetes care company

• By launching dorzagliatin commercially, first in China and then globally

• Either as monotherapy or in combination with approved anti-diabetes drugs

• Employing AI to develop personalized treatment for the entire heterogenic

universe of Type 2 diabetes patients worldwide

A leading, clinical-stage innovative drug development company in China focused on

developing novel therapies for the treatment of diabetes

Mission

Objectives

Strategy

Establish dorzagliatin as the cornerstone therapy for the treatment of

diabetes by restoring glucose homeostasis in Type 2 diabetes patients

Leverage Hua’s internal team and strong partnership network to continue

advancing our current pipeline

Partner with either China-based or international pharmaceutical companies

to make dorzagliatin available to patients, in both China and regions outside

of China

SAIL Ge Li J Baldwin

Founding Investors

Hua Medicine – A Global First-in-Class Biotech

5


Hua Medicine

Global rights to dorzagliatin composition of

matter, chemical process, formulation and

multiple products in FDC with OADs

Met Primary Endpoint in pivotal Phase III

monotherapy trial, for China regulatory

approval purposes

First-in-Class (GKA) drug to significantly

and sustainably reduce HbA1c safely

First Novel Concept addressing impaired

glucose homeostasis - the underlying cause

of T2D

Demonstrated viability in combination with

DPP-4 and SGLT-2 inhibitors

Suitable for T2D patients with kidney

disease

Massive market opportunity – global T2D

population is 453 mm (120 mm in China

alone)

RMB 1.1bn cash as of December 31, 2019

China-Based First-In-Class

Li Chen

CEO & CSO

Bob Nelsen

Chairman

Arch Ventures

2019 Highlights

6


Clinical trials:

Achieved primary efficacy endpoint in a 24-week double blinded placebo controlled Phase III trial in drug

naïve T2D patients in China, with very low hypoglycemia incidents and good safety profile

Completed enrollment in a metformin add on Phase III registration trial

Completed HMM0110, which demonstrated desirable pharmacokinetics profile in patients with end stage chronic

kidney disease, indicating the potential use of dorzagliatin among T2D patients with moderate, severe and end

stage chronic kidney disease (i.e. stages 3-5 of CKD)

Completed HMM0111, investigating the PK and PD parameters of dorzagliatin either alone or in combination with

sitagliptin in T2D patients in the United States, with positive results

Other:

Granted a formulation patent for dorzagliatin in China

Filed six patent applications covering the IPR of fixed dose combination of dorzagliatin with six classes of oral-

antidiabetic drugs

Initiated a formal collaboration with Dr. Franz Matschinsky, recipient of 2020 Rolf Luft Award

Presented AI based machine learning results at the American Diabetes Association’s 79th Scientific Sessions,

providing a non-biased methodology to sub-classify T2D patients

Announced that global operation headquarters and R&D center will be established in Shanghai’s ZhangJiang

Science City

Fully validated cGMP commercial manufacturing processes for API and drug product to support the China launch

of dorzagliatin

Former U.S. FDA Officer Dr. Fuxing Tang joined Hua Medicine as Chief Technology Officer, VP of Formulation

R&D and Product Development

Cash position as of December 31, 2019: RMB 1.1bn

Phase III Topline Results were Presented in the Keynote Lectures of 2019 CDS Plenary Session

7

NH N

N

N

NN


Professor Zhu Dalong, Chairman of CDS, hosting 2019 CDS

plenary session

Professor Zhu Dalong, presenting dorzagliatin Phase III

topline data at the 2019 CDS plenary session

Dr. Yang Wenying, ex-Chairwoman of CDS, attending the

2019 CDS plenary session

2019 CDS Plenary Session audience members

Ongoing Phase III Trials: HMM0301 / HMM0302 Study Design

8

Study Design for: HMM0301: 52-week completed March 2, 2020

Dorzagliatin Mono-therapy Trial for Drug Naïve T2D Patients (463 Patients)

HMM0302: 24-week completed February 16, 2020

Dorzagliatin Metformin Add-on Therapy Trial for Metformin Users (766 Patients)

Screening Placebo Run-in 24 Weeks Double-blind 28 Weeks Open-label Follow-up

~2 Weeks 4 Weeks Treatment Period Treatment Period 1 Week

V1 V2 V3 V4 V5 V6 V7 V8 V9 V10 V11 V12 V13 V14 V15 V16

-4W -1W 0W 4W 8W 12W 16W 20W 24W 28W 34W 40W 46W 52W

HbA1c, FPG

2h-PPG

Safety

Screening Placebo Run-in

0301: HMS5552 75mg BID

0302: HMS5552 75mg BID + metformin

0301: placebo BID

0302: placebo BID + metformin

0301: HMS5552 75mg BID

0302: HMS5552 75mg BID +

metformin

Follow-up

Randomization

Monotherapy – (2:1)

Metformin Add-on – (1:1)

Primary Efficacy Endpoint For

NMPA SubmissionLong-term Safety

Endpoints

Primary endpoint of HbA1c reduction of 0.4% over placebo, p-value < 0.05


Update from COVID-19

9


Clinical Achievements

February 16, 2020: Completed last patient out, 24-week patient visit for HMM0302

March 2, 2020: Completed last patient out, 52-week (plus one week follow-up)

patient visit for HMM0301

Continued strict adherence to national guidelines, and enforced additional

pharmacovigilance and quality control

Other

February 3, 2020: Hua employees returned to work

remotely

March 2, 2020: Hua employees began returning to

offices in China

Things to note

Potential delays in release of top-line results and NDA-

enabling work

2020 Outlook

10


Clinical trial readout:

HMM0301 monotherapy Phase III trial 52-week results

HMM0302 combination with metformin Phase III trial 24-week,

52-week results

Other:

Initiate studies of dorzagliatin for other potential indications

Prepare and finalize NDA submission in China

Expand and prepare commercialization, sales and marketing

team for planned 2021 product launch in China

Engage international and China-based pharmaceutical

companies in discussions regarding partnership for China and

ex-China territory

Dorzagliatin

A First-in-Class Anti-Diabetic Therapy Focused on Treating

the Underlying Cause of Type 2 Diabetes

Most large multinational pharmaceutical companies with a metabolic disease

franchise have tried to create a viable and safe glucokinase activator (GKA) to

treat type 2 diabetes, none have entered phase III

Dorzagliatin is the first GKA to achieve the primary efficacy endpoint with

desirable safety profile at 24-weeks in a Phase III trial

Targeting the glucose sensor role of GK, dorzagliatin is conceptually

differentiated from previous GKA which worked on lowering the blood

glucose and treated GK as a glucose processor only

Current State of the Type 2 Diabetes Landscape

12


Large

market

What is the

unmet

need?

Why hasn’t

anyone else

developed a

GK?

Over 450 million people with type 2 diabetes, globally; 120 million+ in China

alone

Over US$80 billion plus of pharmaceutical sales globally every year

Not one approved drug currently treats the underlying cause of type 2

diabetes – loss of glucose sensitivity and impairment of glucose homeostasis

Restoring the function of impaired glucokinase is the only scientifically

validated means to restore glucose sensitivity in homeostasis

How Do We Stop Type 2 Diabetes?

13


To maintain blood glucose levels within a healthy range,

achieving glucose homeostasis

Goal in treating diabetes:

Lowering blood glucose levels alone will not stop the progressive

degenerative nature of diabetes, leading to complications

T2D is a Progressive Disease with Degenerationof β Cell Function and Increasing Insulin Resistance

14

Source: Vivian Fonseca, Diabetes Care, 2009, Vol 32, S2; Source: J Merier, R Bonadonna Diabetes Care (2013) 36, S1131 Retrospective survey.

Type 2 diabetes is a progressive disease with deterioration of β cells function

Loss of glucose sensitivity in Type 2 diabetes patients is the first step in the progressive destruction of β cells

Impaired β cells function results in hyperglycemia stress which causes progressive damage of β cells

Deterioration of the 1st phase insulin secretion is the leading cause of impaired glucose homeostasis

Patients with Monotherapy: HbA1c Increased by 1%

Every 2 Years, β-Cell Function Decreased Accordingly1

Impaired β-Cell Function Results in Hyperglycemia

Stress which Causes Progressive Damage of β Cells

Hyperglycemia

High FFA

Levels

Increased

Secretory Demand

per -Cell

Oxidative Stress

ER Stress

0

2

4

6

8

10

12

14

0 1 2 3 4 5 6 7 8 9 10 11

A1

C (

%)

Time (Years)

Coefficient of Failure = 0.47 A1c %/year

r2=0.95


• Deficiency in the ability of glucose to trigger insulin release

• Cells have lost glucose sensitivity and early phase insulin

release is reduced

• Reduction in glucose sensitivity is the key culprit behind Type

2 Diabetes

Current Diabetes Medicine Can Not Restore β-cell Function

15

Restoration of glucose sensor function

required


Recent research indicates that we have not solved the fundamental cause of diabetes

Treatment

Group

• Impaired glucose tolerance (IGT)

• Treatment-naïve type 2 diabetes (<12

months)

Treatment

length

• 12-month treatment

• Stop medication for 3 months

• Measure β-cell function at 15 months

Treatment

arms

• Metformin alone (12m)

• Liraglutide (GLP-1) + metformin

• Glargine (3m) + metformin (9m)

• Placebo

Conclusion • Interventions that improved β-cell

function during active treatment failed to

produce persistent benefits after

withdrawal

• Suggests continued intervention may be

required to alter the progressive β-cell

dysfunction

Organs in which GK occurs

BrainMuscles Fat

~5mM ＜4mM ＞10mM

GLP-1

Glucose

Insulin

α cells

β

cells

LiverIntestines

＞5.5mM

Glucose Controls Whole Body Glucose Homeostasis

16

Glucose is a hormone

Glucokinase is a sensor

Glucose Homeostasis is Controlled by Glucose via Glucose Sensor GK

Source: 陈力，2016 《药物进展》

GK Sensor RoleGlucose Storage and

Production

Glucagon

+

++

+

+ +

+

-

-

Glucose

Homeostasis

Glucose is

controlled within a

very narrow

range:

4- 6.5mM

Set point:

5mM


Threshold controlled glucose homeostasis

Fix the Sensor, Control Diabetes

17


Hyper

Hypo

Hyper

Hypo

Glucagon

GLP-1

Acarbose

PPAR

SGLT2

Metformin

Insulin

Dorzagliatin

Cornerstone Control of Glucose Homeostasis

SU

DPPIV

Messenger: glucose level

Set Point: 5 mmol/liter1

Threshold: 4-6 mmol/liter1

Controller: Glucokinase in the pancreas and small intestine-

Glucose Sensor

Effector: insulin, glucagon, GLP-1 (glucagon-like peptide 1)

Operator: hexokinase 1-32, SGLT-2, GKL (Liver GK)

Glucokinase is a Glucose Sensor in Glucose Homeostasis

18

Source: Franz Matschinsky, Mol. and Cell Biology of Type 2 Diabetes and Its Complications, 1998, vol 4, pp 14-291 A common measure of blood glucose levels is hemoglobin A1c, or HbA1c, which measures average glycated blood glucose levels for the 3 months prior to testing. HbA1c levels for people without

diabetes is between 4% and 5.6% (equivalent to 4-5.6 mmol/liter), for people with impaired glucose tolerance (IGT), or pre-diabetics, is between 5.74% and 6.4% (equivalent to 5.74 -6.4 mmol/liter)

and for people with diabetes is 6.5% or higher (equivalent to 6.5 mmol/liter or higher).2 In addition to GK (also referred to as hexokinase type 4), Hexokinase types 1-3 play a role in the glucose homeostasis process. Unlike a properly functioning GK, which is only active at blood

glucose levels over 5.5 mmol/liter, hexokinase types 1-3 are active in the presence of even small amounts of glucose in the bloodstream – providing as a bodily survival mechanism needed energy

to the brain, muscles and other core bodily functions.

When the sensor malfunctions or is impaired, automatic control is lost

Messenger: air temperature

Set Point: 22o Celsius

Threshold: 21-23o Celsius

Controller: Thermo Sensor (thermostat)

Effector: Electronic signal

Operator: Heater, Cooler, Ventilator

Operation

Cooler

Heater

Ventilator

Operation

Insulin / GLP-1

Glucagon

Liver GK

Glucose Homeostasis in Human Body Thermostat in a Building


Key Recognitions of Glucokinase

19

Discovered in the 1960s

Published in Science Magazine in 2003 by Dr. Franz Matschinsky, “Godfather of

Glucokinase”, in collaboration with Roche

Partner with Hua Medicine in advancing GKA

Winner of Rolf Luft Award 2020

Science 2003:

Allosteric Activators of Glucokinase: Potential Role in Diabetes Therapy

“In several rodent models of type 2 diabetes mellitus, GKAs lowered blood glucose levels,

improved the results of glucose tolerance tests, and increased hepatic glucose uptake. These

findings may lead to the development of new drug therapies for diabetes.”


Source: Franz Machinsky et al . Science: Vol 301, Issue 5631, 18 July 2003

Rolf Luft Award 2020 awarded to Dr. Franz Matschinsky by Karolinska

Institutet

For the discovery that glucokinase (GK) is the sensor controlling glucose-stimulated

insulin secretion in the pancreatic β-cell and initiating GKA discovery

Dorzagliatin Has the Potential to Repair the Glucokinase Glucose Sensor

20

T2D Patients Disposition Index

(0.1)

0.0

0.1

0.2

0.3

0.4

12 Week 13 Week

Med

ian

Ch

an

ge f

rom

Baseli

ne

of

DI

Placebo 75mgBID

P=0.0461

P=0.0387

Phase II

0

2

4

6

8

0 1 2 3 4100mg_Day -1

100mg_Day 7

0

2

4

6

8

0 1 2 3 450mg_Day -1

50mg_Day 7

Hours

C-P

ep

tid

e L

evel

(ug

/L)

0

2

4

6

8

0 1 2 3 4Placebo_Day -1

Placebo_Day 7

0

2

4

6

8

0 1 2 3 425mg_Day -1

25mg_Day 7

Meal

T2D Patient Early-stage insulin release Phase Ib

T2D Patient Early Insulinogenic index

0.05 0.050.06

0.10

0

0.05

0.1

0.15

75mg BID 75mg QD

ΔC

30/Δ

G30

Baseline Day 32

24.66%

167.67%*

Phase Ic

Type 2 Diabetes Rat Pancreas

0

15

30

45

60

75

90

Control Diabetic HMS-L HMS-H

Nu

mb

er

of

Ins

uli

n-

Imm

un

op

os

itiv

e C

ell

s

(b)

Control

HMS-L HMS-H

Diabetic

Pre-clinical


November 2019: HMM0301 Phase 3 Topline Results

21


First drug candidate focused on the underlying cause of type 2 diabetes, glucose sensing,

to meet its primary efficacy endpoint over 24 week Phase III trial

1.07% HbA1c reduction from baseline of 8.35% in dorzagliatin treated group compared to 0.5%

HbA1c reduction from baseline of 8.37% in placebo group (p-value < 0.0001)

45.4% of patients treated with dorzagliatin achieved target HbA1c level of 7.0% or less at 24-

weeks compared to 21.5% of patients treated with placebo (p-value < 0.0001)

Patients treated with dorzagliatin achieved homeostasis control rate of 45.0% compared with

21.5% in placebo group (p-value < 0.0001)

Dorzagliatin was well tolerated and had a good safety profile

No death, no drug-related serious adverse event over 24 week

Less than 1% incidence of hypoglycemia over 24 week and no severe hypoglycemia

The 28 week open label safety outcome trial of HMM0301 is complete — Last patient out

was March 2, 2020

HMM0301 Phase III 24-week topline results in Chinese drug-naïve patients with Type 2 Diabetes

(10.3%)

(10.3%)

(33.1%)

(33.1%)

January 2020: Positive Results of HMM0111 Validates the Synergy of DPP-4 and GKA

22

Post Prandial Glucose Level

Note: AUEC represents area under the effect curve

AUEC (0-4hr) Co-administration orally of dorzagliatin and

sitagliptin at steady state demonstrated no

impact on their PK properties

OGTT showed synergy in glucose lowering effect

over both monotherapies

It has also demonstrated that dorzagliatin add-on

to sitagliptin increases C-peptide secretion over

dorzagliatin and sitagliptin alone, suggesting a

synergistic effect of improved β-cell function.

Compared to sitagliptin, Dorzagliatin showed clear advantage on post-prandial glucose level (PPG) control in 0-4 hr in the Oral Glucose

Tolerance Test (OGTT) study

Dorzagliatin + sitagliptin gives the best effect on overall PPG reduction

15 patients were included in the trial.

378339

253

0

100

200

300

400

500

600

AU

EC

0-4

h(h

r*m

g/d

L)

Sitagliptin

(100mg QD)

Dorzagliatin

(75mg BID)

Sitagliptin (100mg QD)

+

Dorzagliatin (75mg BID)

Phase I U.S. Drug-drug

Interaction Trials


-33% (p<0.01)

-10% (p<0.01)

Jan 2020: Positive Results of HMM0110

23

Study:

HMM0110 was conducted in China to evaluate whether dorzagliatin can be readily used in Type 2

diabetes (T2D) patients with impaired renal function.

Conclusion:

In subjects with end stage renal disease and are not on dialysis, the study indicated no

significant impact on PK properties subjects exposed to dorzagliatin.

This result supports dorzagliatin as a promising solution and potential supplementary

option for T2D patients with moderate, severe and end stage chronic kidney disease (i.e.,

stages 3-5 of CKD) which can provide satisfactory blood glucose control safely and without

dose adjustment.

Most of current oral antidiabetic drugs are not readily suitable for patients with renal impairment,

especially at moderate, severe and end stages, as current oral treatments either require dose

adjustment (e.g., metformin and the top-selling DPP-4 inhibitors) or are contraindicated (e.g.,

SGLT-2 inhibitors).

Stage 3-5 CKD patients of T2D patients in China is about 21.9%


Jan 2020: Positive Results of HMM0110 Supports the Potential of Dorzagliatin in T2D Patients with

Moderate, Severe and End Stage Chronic Kidney Disease (i.e. stages 3-5 of CKD)

(10.3%)

(10.3%)

(33.1%)

(33.1%)

April 2020: Positive Results of HMM0112 Validates the Synergy of SGLT-2 and GKA

24


Note: AUEC represents area under the effect curve

AUEC (0-4hr)

Co-administration orally of dorzagliatin and

empagliflozin at steady state demonstrated no

impact on their PK properties

OGTT showed synergy in glucose lowering effect

over both monotherapies

It has also demonstrated that dorzagliatin add-on

to empagliflozin increases C-peptide secretion

over dorzagliatin and empagliflozin alone,

suggesting a synergistic effect of improved β-cell

function.

452

364

279

0

100

200

300

400

500

600

AU

EC

0-4

h(h

r*m

g/d

L)

-23% (p<0.05)

Compared to empagliflozin, dorzagliatin showed clear advantage on post-prandial glucose level (PPG) control in 0-4 hr in the Oral Glucose


Dorzagliatin + empagliflozin gives the best effect on overall PPG reduction

15 patients were included in the trial.

Empagliflozin

(25mg QD)

Dorzagliatin

(75mg BID)

Empagliflozin (25mg QD)

+

Dorzagliatin (75mg BID)


Interaction Trials


-38% (p<0.0001)

A proprietary algorithm is developed at Hua Medicine based on clinically validated biomarkers

Potential as Cornerstone Therapy for Personalized Diabetes Care

25

1 The Type 2 diabetes (T2D) patients are classified into 6 different subtypes: low insulin resistance (LIR), severe insulin resistance (SIR), SIR with diminished β-cell function

(SIR_ β∆), severe impaired glucose intolerance (SIGT), SIGT with diminished β -cell function (SIGT_ β∆), and IR with severely diminished β -cell function (SIR_Sβ∆)

Source: Poster 2019 ADA Scientific Sessions

Dorzagliatin has the potential to serve as the next generation cornerstone treatment of T2D

– Personalized diabetes care in progress with novel algorithm development

Personalized Type 2 Diabetes Medicine: A Comprehensive Solution for Diabetes Patients

T2D_A

LIR

T2D_B

SIR

T2D_C

SIR_β∆

T2D_D

SIGT

T2D_E

SIGT_β∆

T2D_F

SIR_Sβ∆

Personalized

Type 2

Diabetes

Care

SolutionHua

Algorithm

Type 2 diabetes

(T2D) Patients1

Drug naive OAD combo Injectable

Dorzagliatin MonoDorzagliatin +

Metformin

Dorzagliatin

+ SGLT-2 or

DPP-4

Dorzagliatin

+ GLP-1 or

insulin

IGT

GCK

Impaired

Pre-

diabetic

Dorzagliatin


AI based machine learning results: providing a non-biased methodology to sub-classify T2D patients

SGLT-2

Metformin

PPAR

DPP-4

GLP-1

AGI

Insulin

Dorza

+

Metformin

tolerated

T2D_CV

T2D_ND

T2D

Obesity

AGI

tolerated

T1D Severe

T2D Severe

T2D NASH

Extended

Injectable

Activates

26

Repair Sensor, Adopt Combo Therapy & Rebuild Homeostasis


First-line in China for IGT driven T2D patients

Combination therapy: FDC with 6 classes OAD covers major T2D patients

Endogenous GLP-1 combo with DPP-4 inhibitors: additional indication in ND

Combo with SGLT-2: T2D with metabolic syndrome

Insulin sparing when add-on to late stage diabetes

Dorzagliatin profile

27


Priority

attributes

Secondary

attributes

Key

opportunity

Restore glucose homeostasis——optimize time-in-range

Protect β-cells and β-cell function

HbA1c reduction with advanced glycemic control

No/Limited hypoglycemia

No GI side effect

T2D with diabetic kidney disease

Sustained efficacy

Limited side effects/no major adverse effects

Neurodegeneration disease benefits

28


Hua Medicine R&D Pipeline

Study Results Coming in the Next 12 Months

29


4

1

2

3

Hua & Partners

Highly Experienced R&D Team with Extensive Chinaand Global Pharmaceutical Experience

Founder & CEO

Li Chen, Ph.D., Founder & Board Director

CSO and Founding Director of Roche R&D Center (China), responsible for development of

China’s drug discovery strategy, creation of discovery portfolio and management of operations

Former head of HTS technology atRoche

Adjunct professor at Tongji University, Ph D advisor

Over 90 publications and patents in basic research and medical sciences

31


Yilei Fu, BS, MBA

VP, Quality Assurance

Daniel Du, Ph.D., MD

SVP, RCM

Jin She, Ph.D.

VP, Chemistry CMC

George Lin

EVP, CFOYi Zhang, Ph.D., MD

SVP, ClinicalR&D

Wenjie Xu, BS, MBA

VP, Commercial

Strategy and Marketing

Haoliang Song, PhD

Sr Director

Non-ClinicalSafety

Shuang Ren, Ph D

Sr Director

Clinical Pharmacology

FuxingTang, Ph.D.

VP, CTO, Chemistry CMC

World-renowned Advisors and Influential Key Opinion Leaders

32

Chinese KOLsAdvisors

Franz Matschinsky, M.D.

Professor of biochemistry and biophysics at the University

of Pennsylvania, Perelman School of Medicine

Founded Penn Diabetes Research Center of the

University of Pennsylvania

Founder of the Islet Cell Biology Core in the University of

Pennsylvania

Received Banting Award (1995), Rolf Luft Award (2020)

Formulated the glucokinase glucose sensor concept

“Glucokinase is a glucose sensor, diabetes gene and

drug target”

Xiaoying Li, MD, Ph.D.

Director of Endocrinology, Zhongshan Hospital

Vice President, Chinese Diabetes Society

Published articles in numerous prestigious journals such as the Lancet Diabetes and Endocrinology，Cell

Metabolism

Dalong Zhu, M.D.

Director of Endocrinology, Nanjing Drum Tower

Hospital

Current President, Chinese Diabetes Society

Published articles in numerous prestigious journals such as the Lancet Diabetes and Endocrinology，Diabetes

Wenying Yang, M.D.

Director of Endocrinology, Director of Department of

Internal Medicine, Vice Chairman of Ethics Committee

at China-Japan Friendship Hospital

Ex President, Chinese Diabetes Society

Published articles in numerous prestigious journals

such as New England Journal of Medicine, Lancet

Diabetes and Endocrinology

Ralph A. DeFronzo, M.D.

Professor and Division Chief of Diabetes Division at the

University of Texas Health Science Center

Deputy Director of Texas Diabetes Institute

Led the U.S. development of metformin, and FDA

approval in 1995

Discovered a new approach to diabetes treatment that

targets glucose reabsorption in the kidneys, which led to

the development and approval of SGLT-2

Received several prestigious awards, including the Lilly

Award (1987) by the American Diabetes Association,

Banting Lectureship Award (1988) by the Canadian

Diabetes Association, Novartis Award (2003), ADA’s

Albert Renold Award (2002), the ADA’s Banting Award

(2008), and the Harold Hamm International Prize (2018)

Published over 800 articles in peer-reviewed medical

journals


A Blue Chip Board

Li Chen George Lin

Chairman

Robert Nelsen Lian Yong Chen

William Keller Alec TsuiWalter Kwauk Junling Liu

33

FIL Capital

Management (Hong Kong)


Hua Suppliers & Partners

34


High quality drug development partners

WuXi AppTec Discovery NCD Clinical CMC

TigerMed Regulatory Clinical

dMed Data Mgmt PV

Covance

Desano Discovery CMC

Frontage Clinical

Jiuzhou CMC

Envigo NCD

Regulatory Clinical

Industry-wide Recognition

35


In 2016, Hua obtained the Annual R&D Achievement Award of the 7th

BayHelix Association Chinese Medicine Award

In 2017, Hua was awarded the first China (Shanghai) Free Trade Zone System

Pilot Program Innovation Representative Enterprise

In 2018, Hua Medicine was awarded the 2017 Innovation and

Entrepreneurship Award by the Pudong New Area People’s Government

In 2018, Dr. Li Chen was selected as one of the 40 Most Influential People in

the Pharmaceutical Industry, in celebration of the 40th Anniversary of Economic

Reform and Opening Up

In 2018, dorzagliatin's Phase II results were published in The Lancet Diabetes

and Endocrinology, Dr. Dalong Zhu and Dr. Li Chen, etc., and were awarded the

"Most Influential Research Awards" in the Chinese Diabetes Society’s 2018

China Top 10 Diabetes Research

In 2019, Dr. Li Chen was appointed as part-time researcher in the new drug

industry of Shanghai Institute of Materia Medica, Chinese Academy of Sciences

In 2019, Dr. Li Chen was appointed as a Director of the Biomedical Commission

in the Shanghai Economic and Information Bureau of the 2nd Shanghai Youth and

Intellectuals Association

Financial Review

Financial Summary

37


Cash Balance: RMB1,105.6 million of cash at 12/31/2019 vs. 1,443.3 million at 12/31/2018.

Total cash decrease of RMB337.7million, consisted of

• Net cash used in operating activities was RMB342.1 million

• Net cash used in investing activities was RMB9.5 million

• Net cash used in financing activities was RMB1.2 million.

• Net effect of exchange rate changes was RMB15.1 million

1,443.31,105.6

2018 2019

(RMB’ million)

Net cash used in operation activities of RMB342.1 million mainly includes cash payment of RMB 238.3

million for the research and development activities and of RMB46.3 million for the administrative

workforce employment.

Financial Summary- continued

38


Research and development expenses of

RMB321.9 million in 2019 vs. RMB269.1 million

in 2018

• an increase of RMB25.3 million related to the

progress of our Phase III clinical trials and

additional Phase I clinical trials conducted in

2019

• an increase of RMB32.6 million associated

with headcount increase and milestone bonus

payments and share-based payments

Administrative expenses of RMB146.6 million

in 2019 vs. RMB100.4 million in 2018

• increase related to the establishment of our

finance and corporate development team and

commercial strategy and marketing team,

• Increase in activities associated with market

research and ongoing public listing costs in

2019

Financial Summary- continued

39


Other income of RMB29.6 million in 2019 vs. RMB10.4 million in 2018

• an increase of RMB13.1 million in government grants

• an increase of RMB6.1 million in bank interest income from short-term time deposits.

Other gains of RMB16.3 million in 2019 vs.RMB63.8 million in 2018

• Smaller appreciation of the U.S. dollar against the RMB in 2019

Loss before tax of RMB425.3 million in 2019, compared to RMB3,604.0million in 2018

• 2018 included RMB3,266 million of loss in fair value of convertible redeemable preferred shares

before the listing date in 2018.

Adjusted net loss* of RMB350.9 million in 2019, compared to RMB279.3 million in 2018.

* Adjusted net loss was calculated by taking loss before tax for the year and adding back (a) share-based payments; and (b) loss on changes in

fair value of financial liabilities at FVTPL.

Appendix

Study Phase Objectives Country

Number of

Subjects Completion Date

HMM0101 Phase IaSingle dose study in healthy subjects to evaluate

safety, and PK/PDChina 60 January 2014

HMM0102 Phase Ib5.5 day multiple-dose study in Type 2 diabetes

subjects to evaluate safety, and PK/PDChina 53 October 2014

HMM0103 Phase Ic

Four-week multiple-dose study (75 QD and 75

BID) in Type 2 diabetes subjects to evaluate

safety, efficacy, and PK/PD

China 24 February 2015

HMM0104 Phase IA drug-drug interaction with metformin in Type 2

diabetes subjects to evaluate DDI, and PK/PDUnited States 15 November 2015

HMM0105 Phase I A mass balance study in healthy subjects United States NA April 2017

HMM0107 Phase IA drug-drug interaction with CYP3A inhibitor

itraconazole in healthy subjectsChina NA December 2017

HMM0108 Phase IA drug-drug interaction with CYP3A inducer

rifampin in healthy subjectsChina NA April 2018

HMM0110 Phase IPhase I study to evaluate impact of renal

impairment on Dorzagliatin PKChina 16 December 2019

HMM0111 Phase IA drug-drug interaction with sitagliptin in Type 2

diabetes subjects to evaluate DDI, and PK/PDUnited States 15 December 2019

HMM0201 Phase II12-week multiple-dose study in Type 2 diabetes

subjects to evaluate safety, efficacy, and PK/PDChina 258 August 2016

Total 10 trials 449 Patients

Hua Has Conducted Comprehensive Clinical Trials

41


Dorzagliatin Demonstrated Excellent Human PK Properties and Targeted Organ Distribution

42

Ph 1a & 1b Combined, 5mg – 200mg

Source: Li Chen, Y Zhang et al ADA 75th Scientific Session, June 5-9, 2015, Boston

Note: AUCinf represents area under a plasma concentration-time curve from the time of administration to infinity, while Cmax represents maximum concentration

Phase Ia and Ib

Dorzagliatin showed very well-behaved and predictable PK profile, linear correlation of dose vs exposure

Dorzagliatin augments glucose sensor functions in pancreas α, β cells and intestine L cell

Dorzagliatin also exhibited a half-life of eight to ten hours, supporting a twice daily regimen

Phase Ib included 53 Type 2 diabetes patients with 10 randomized on placebo

0

5,000

10,000

15,000

20,000

0 25 50 75 100 125 150 175 200

Exp

os

ure

Dose (mg)

Cmax (ng/mL) AUCinf (h*ng/mL)


Dorzagliatin Modulates GK Function as Glucose Sensor

43

Phase Ia trial targeted healthy adults in China with a single ascending dose (SAD)

Patients were fasted over night and having HMS5552 next morning at time hr 0, continued fasting till hr 4 when meal is given

Dose dependent reductions in glucose and increases in insulin secretion when fasting plasma glucose levels and post-prandial

plasma glucose levels were measured during the four hours prior to a meal, and in the two hours after

Phase Ia included 60 healthy volunteers in six treatment groups with different dosages

3.00

4.00

5.00

6.00

7.00

8.00

9.00

(0.5

)

(0.2

5) 0

0.2

5

0.5 1 2 3 4

4.2

5

4.5 5 6

Glu

co

se L

ev

el (m

mo

l/L

)

Time (hour)

Placebo 5mg 10mg 15mg

25mg 35mg 50mg

Fasting (0~4hr)Meal (at 4hr)

0

20

40

60

80

100

120

140

(0.5

)

(0.2

5) 0

0.2

5

0.5 1 2 3 4

4.2

5

4.5 5 6

Ins

ulin

Le

vel (u

U/m

L)

Time (hour)

Placebo Low Dose (5mg~15mg)

High Dose (25mg~50mg)

Fasting (0~4hr)Meal (at 4hr)

Phase Ia


0%

10%

20%

30%

40%

50%

60%

Peak C

-pep

tid

e R

esp

on

se (

%)

Time Post Oral Glucose Load (min)

NGT IGT T2D

Dorzagliatin Resets the Thresholds in T2D Patients with Improved Glucose SensitivityProof of Mechanism of Action in Phase I Study

44

Source: R.W.Bergstrom J. Clin. Endocrinol. Metab. (1990), 71(6):1447-53

Source: DL Zhu, Y. Zhang, L Chen et al ADA 75th Scientific Session, June 5-9, 2015, Boston

Impaired threshold of GSIR in IGT and T2D patients Dorzagliatin resets the threshold of GSIR in T2D patients

012345678

0 1 2 3 4

Placebo_Day -1

Placebo_Day 7

012345678

0 1 2 3 4

25mg_Day -1

25mg_Day 7

012345678

0 1 2 3 4

100mg_Day -1

100mg_Day 7

012345678

0 1 2 3 4

50mg_Day -1

50mg_Day 7

Hours Hours

C-P

ep

tid

e L

ev

el

(ug

/L)

C-P

ep

tid

e L

ev

el (u

g/L

)

Meal

Phase Ib

30 18060 90 120


Dorzagliatin Reduces Hypoglycemia Risk by improving α-cell Sensitivity

45

Source: DL Zhu, Li Chen et al ADA 75th Scientific Session, June 5-9, 2015, Boston

Note: Each dose group had 10 patients, with 2 placebo and 8 treatment patients in each. According to the American Diabetes Association, A1c below 3.9 mmol/liter means

“hypoglycemia alert value.” This is distinct from “clinically significant hypoglycemia,” which is A1c below 3 mmol/liter

Note: Dosages were administered on day 1, and days 3-8.

Phase Ib

Patients showed significant reduction in FPG, with no severe hypoglycemia

0

2

4

6

8

10

12

0 1 2 3 4

FPG Glucose Level in Different Dosages

150mg 200mg

0

2

4

6

8

10

12

0 1 2 3 4

Hour Hour

FPG > 3.9mM/L FPG > 3.9mM/L

Day -2 Day 3 Day 8

FP

G L

ev

el (m

mo

l/L

)


•Oral doses were given to patties fasted overnight over 10 hours

•Measures FPG level for additional 4 hour post dose

•No server hypoglycemia at 200 mg BID, but significant reduction of FPG

Proof of Concept Personalized Type 2 Diabetes Medicine

46

Proof of Concept — Personalized Type 2 Diabetes Medicine

1 Oral Glucose Tolerance Test

24

20

200

28 day treatment

75 mg QD

75 mg BID

Chinese T2D Patients

Naive or OAD treated

D HbA1c > 0.6%*

Improve β cell function

Well tolerated

Response rate: > 80%

OGTT1

*HbA1c treatment

standard by ADA

Step

By

Step

HbA1c: 7 – 11%

FPG: 7.0 – 16 mM

TG < 8.0 & BMI < 35

HbA1c

FPG

TG & BMI

HOMA-b

HOMA-IR

DI30/G30


Phase Ic

Dorzagliatin Showed Best Effect Combining with Metformin

47Note: AUC represents area under the curve, while AUEC represents area under the effect curve； SD represents mean standard deviation


Glucose AUC (0-4hr)

Demonstrated no drug- drug interaction between

Dorzagliatin and metformin

Demonstrated synergies in the glucose lowering

potential of the combination of Dorzagliatin plus

metformin as compared to either metformin or

Dorzagliatin as a monotherapy

Compared to metformin, Dorzagliatin showed clear advantage on post-prandial glucose level (PPG) control in 0-4 hr in the Oral Glucose


Dorzagliatin + Metformin gives the best effect on overall PPG reduction

No hypoglycemia adverse effects in the study

15 patients were included in the trial for treatment of 13 days

110.2

73.0

46.7

0

20

40

60

80

100

120

AU

EC

0-4

h(h

r*m

g/d

L)

Metformin

(500mg)

Dorzagliatin

(50mg)

Metformin (500mg)

+

Dorzagliatin (50mg)


Interaction Trials


(0.31)

(0.47)

(0.69)¹

(0.79)²

(1.12)³(1.6)

(1.4)

(1.2)

(1.0)

(0.8)

(0.6)

(0.4)

(0.2)

0.0

Placebo 75mgQD 100mgQD 50mgBID 75mgBID

Sustained Efficacy in HbA1c ReductionProof of Concept in Phase II Study

48

1 P<0.05 compared to placebo group. 2 P<0.01 compared to placebo group. 3 P<0.001 compared to placebo group. 4 LOCF represents for “last observation carried forward”. 5 The averages calculated applied least-square mean averages. 6 The averages calculated applied mean square averages.

(1.50)

(1.25)

(1.00)

(0.75)

(0.50)

(0.25)

0.00

0 2 4 6 8 10 12

Placebo 75mgQD 100mgQD

50mgBID 75mgBID

Double blinded, placebo controlled and randomized Phase II trial with 258 patients in China over 22 clinical centers

Published in Lancet in May 2018...with the 75 mg BID group showing HbA1c reduction effect

starting from week fourDorzagliatin reduced HbA1c levels dose dependently...

Hb

A1c C

han

ge f

rom

Baselin

e (

%)

Hb

A1c C

han

ge f

rom

Baselin

e (

%)

Dorzagliatin: Proof-of-Concept (POC) Achieved with Sustained Efficacy

The chart above showcases HbA1c change from baseline after the

12-week treatment period (PPS, LOCF4)5, with the results showing

that Dorzagliatin reduced HbA1c levels dose dependently with 75

mg QD, 100 mg QD, 50 mg BID and 75 mg BID, after the treatment

period

In the 75mg BID group, both fasting plasma glucose level (FPG) and

post-prandial glucose level (PPG) were well controlled without

increasing hypoglycemia or dyslipidemia risk

The chart above showcases HbA1c change from baseline over time

(PPS)6

Results showed that HbA1c reduction was significant starting from

week four, and continued in weeks eight and 12

Phase II


Drug Naive Patients Achieved Better HbA1c Reduction in Phase II Trial

49

HbA1c Reduction in OAD Patients HbA1c Reduction in Drug Naive Patients

Notes:

P<0.05 compared to Placebo group

OAD or Naive / NumberHbA1c Reduction from Baseline (%)

Placebo 75 mg QD 100 mg QD 50 mg BID 75 mg BID

OAD 34/31/28/32/27 (0.41) (0.15) (0.42) (0.70) (0.97)*

Drug Naive 19/22/22/18/22 (0.17) (0.85)* (0.95)* (1.04)* (1.21)*

Type 2 diabetes drug naive patients achieved better HbA1c reduction in all active groups

75mg BID works well in both drug naive and OAD patients

(1.50)

(1.25)

(1.00)

(0.75)

(0.50)

(0.25)

0.00

0 2 4 6 8 10 12

Hb

A1

c C

ha

ng

es

fro

m B

as

eli

ne

(%

)

week


(1.50)

(1.25)

(1.00)

(0.75)

(0.50)

(0.25)

0.00

0 2 4 6 8 10 12

Hb

A1

c C

ha

ng

es

fro

m B

as

eli

ne

(%

)

week


Phase II


50

Note: Data are n(%). AE=adverse event. SAE=serious adverse event. WBC=white blood cells. HDL = High-density Lipo protein1 Drug-related AE: means AE that the investigator judged as Probably Related or Possible Related to the investigational drug; One patient was counted at most once per

category; One patient may be counted in multiple categories

Dorzagliatin is well tolerated with low

hypoglycemia incidence and low drug-

related adverse events

The incidence of adverse events (AE) reported

in all 5 treatment groups was similar

No drug-related serious AE (SAE) or severe

hypoglycemia

No identified causal relationship between

groups and AE incidence; no confirmed

HMS5552 dose-related AEs

No clinically significant laboratory, vital sign,

physical examination or electrocardiograms

(ECG) abnormalities

Dorzagliatin shows lipid and body weight

neutral profile

No occurrence of drug-related SAEs or severe hypoglycemia as demonstrated by the

Treatment-Emergent Adverse Event (TEAE) Overview belowDorzagliatin is Safe and Well Tolerated

Phase II

Satisfactory Safety Data Observed and EvidencedProof of Concept in Phase II Study

Placebo

(n=53)

75 mg Once

daily (n=53)

100 mg

Once

Daily (n=50)

50 mg Twice

Daily (n=51)

75 mg Twice

Daily (n=51)

Active Total

(n=205)

Any AE 27 (51%) 30 (57%) 31 (62%) 24 (47%) 27 (53%) 112 (55%)

Mild AE 27 (51%) 27 (51%) 31 (62%) 22 (43%) 25 (49%) 105 (51%)

Moderate AE 2 (4%) 3 (6%) 2 (4%) 3 (6%) 3 (6%) 11 (5%)

Severe AE 0 1 (2%) 0 1 (2%) 0 2 (1%)

Any SAE 0 1 (2%) 1 (2%) 1 (2%) 0 3 (2%)

Drug-related1 AE 1 (2%) 5 (9%) 6 (12%) 6 (12%) 3 (6%) 20 (10%)

AE Leading to Drug Discontinuation 0 1 (2%) 0 2 (4%) 0 3 (2%)

Drug Related1 0 0 0 1 (2%) 0 1 (1%)

Not Drug Related 0 1 (2%) 0 1 (2%) 0 2 (2%)

AE Occurring in 5% of Patients in

Any Group

Upper Respiratory Tract Infection

3 (6%) 6 (11%) 6 (12%) 1 (2%) 4 (8%) 17 (8%)

Hyperuricaemia 2 (4%) 3 (6%) 6 (12%) 3 (6%) 4 (8%) 16 (8%)

Dizziness 0 2 (4%) 4 (8%) 4 (8%) 0 10 (5%)

Protein Present in Urine 1 (2%) 3 (6%) 2 (4%) 0 2 (4%) 7 (3%)

Urinary Tract Infection 3 (6%) 1 (2%) 3 (6%) 0 1 (2%) 5 (2%)

Blood Creatine Phosphokinase

Increased5 (9%) 0 1 (2%) 1 (2%) 1 (2%) 3 (1%)

WBC Urine Positive 1 (2%) 1 (2%) 0 2 (4%) 3 (6%) 6 (3%)

Hepatic function Abnormal 1 (2%) 2 (4%) 1 (2%) 3 (6%) 0 6 (3%)

HDL Decreased 1 (2%) 1 (2%) 0 1 (2%) 4 (8%) 6 (3%)

Ventricular Extrasystole 0 0 1 (2%) 0 3 (6%) 4 (2%)

Nasopharyngitis 0 0 1 (2%) 3 (6%) 0 4 (2%)

Hypoglycaemia (≤3.9 mmol/L) 0 3 (6%) 2 (4%) 3 (6%) 3 (6%) 11 (5%)

Hypoglycaemia (≤3.0 mmol/L) 0 1 (2%) 0 0 1 (2%) 2 (1%)


High HbA1c Control Rate and Response Rate AchievedProof of Concept in Phase II Study

51

All Dorzagliatin treatment groups achieved significant HbA1c response compared with placebo, with 44.9% achieving reduction of HbA1C to <7% and 75.0%

achieving 10% and above reduction. The results have been published on Lancet

50 mg BID1 and 75 mg BID1 showed excellent HbA1c response rates and target rates

13.2%

30.2%

32.0%

44.0%

44.9%

0% 10% 20% 30% 40% 50% 60%

Placebo

75mgQD

100mgQD

50mgBID

75mgBID

Rates of Achieving Glycemic Control and Treatment Response as Measured by HbA1c Changes

Both 50 mg BID and 75 mg BID groups showed

excellent HbA1c control rate (HbA1c < 7.0%) 2

The same two treatment groups also showed excellent HbA1c

response rate (HbA1c change > 10% reduction from baseline)2

1

1

1

1

The chart above showcases HbA1c response rate at week 12 (FAS),

with the criteria being achieving HbA1c reduction of >10% at week 12

75.0% of the 75 mg BID group patients were able to reduce their

HbA1c baseline levels by greater than 10% by week 12

1 BID denotes “bis in die” (twice a day), while QD denotes “quaque die“ (once a day). 2 Full analysis set (FAS) data.

The chart above showcases HbA1c control rate at week 12 (FAS),

with the criteria being achieving glycemic control as measured by

HbA1c < 7.0% at week 12

44.9% of the 75 mg BID group patients achieved target clinical

response

28.0%

48.8%

55.6%

67.4%

75.0%

0% 20% 40% 60% 80%

Placebo

75mg QD¹

100mg QD¹

50mg BID¹

75mg BID¹

Phase II


Compelling Sets of Composite Endpoint Observed

52

Source: “Achieving a clinically relevant composite outcome of an HbA1c of <7% without weight gain or hypoglycemia in Type 2 diabetes: a meta-analysis of the liraglutide clinical trial programme” by

B. Zinman et al Diabetes, Obesity and Metabolism 14:77-82, 2012

Note: Dorzagliatin data was from Phase II trial conducted over 12 weeks, while the study comparison was conducted on 26 week clinical trials.

35%

26%

22%

15%

9%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

75m

g B

ID

50m

g B

ID

100

mg Q

D

75m

g Q

D

Pla

ce

bo

40%

32%

25%

15%

11%8% 8%

6%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

Lira

1.8

mg

(GL

P-1

)

Lira

1.2

mg

(GL

P-1

)

Exen

atid

e(G

LP

-1)

Gla

rgin

e

Sitag

liptin

(DP

P-4

)

Su

lph

onylu

rea

Pla

ce

bo

Th

iazo

lidin

ed

ion

e

Pa

tie

nts

Rea

ch

ing

Co

mp

os

ite

Ou

tco

me

fo

r H

bA

1c

<7

.0%

, n

o H

yp

og

lyc

em

ia a

nd

no

We

igh

t G

ain

(%

)

Injections PlaceboOral

...compared with other Type 2 diabetes treatment composite

endpoints over 26-week treatment periods

Favorable composite response rate of Dorzagliatin

in a 12-week treatment period...

The composite response rate of Dorzagliatin in a 12-week treatment reached 35.4% in the 75 mg twice daily group and

demonstrated its favorable profile in glucose reduction, as well as low risk of hypoglycemia and weight gain

The clinical trial results have been published on Lancet

In the trial, the 75 mg BID group reached a composite response rate of 35.4% over a 12-week treatment period, which compares favorably with other treatment

methods tested over a 26-week period

Phase II


Dorzagliatin Improved β-cell function and Reduced Insulin Resistance

53

Reduced Insulin Resistance Improved β-cell Function

Note: HOMA-IR represents homeostatic model assessment – insulin resistance, while DI measures β-cell function

One week after the conclusion of the trial, patients continue to see sustained effect in the HOMA-IR and Disposition Index

Improves pancreatic β-cell function

Reduces insulin resistance

Chinese drug naive Type 2 diabetes

patients 3 month treatment

(2.0)

(1.5)

(1.0)

(0.5)

0.0

12 Week 13 Week

Med

ian

Ch

an

ge f

rom

Baselin

e o

f H

OM

A-I

R

Placebo 75mgBID

P=0.0307P=0.0240

(0.1)

0.0

0.1

0.2

0.3

0.4

12 Week 13 Week

Med

ian

Ch

an

ge f

rom

Baselin

e o

f D

I

Placebo 75mgBID

P=0.0461

P=0.0387

Phase II


Sources:

• Study 1: Lingyu He et al, Differential HbA1c response in the placebo arm of DPP_4 inhibitor clinical trials conducted in China compared to other countries: a systematic view and meta-analysis. BMC Pharmacology and

Toxicology (2016) 17:40 • Study 2: LinongJI,, et al, 中国2型糖尿病患者中的安慰剂效应, 《中国糖尿病杂志》， 2015，Vol 7, p 35.

Comparison with Efficacy Results of other Anti-Diabetic Drugs in their First Phase III studies

54


Phase III Monotherapy Treatment Studies of the First-In-Class T2D therapies

(1.07)

(0.50)

(1.3)

(0.8)

(0.3)

0.2

Dorzagliatin Placebo

China trials Global trials

(0.61)

(0.90)

(0.77)

(0.90)

0.18

(0.20)

0.14

(0.20)

(1.3)

(0.8)

(0.3)

0.2

Sitagliptin Dapagliflozin Canagliflozin Exenatide

Treatment Placebo

Drug Dorzagliatin Sitagliptin

Randomized Number 463 744

Duration (weeks) 24 24

Anti-diabetic Drug historyDrug-naive

Drug naïve or washed out

therapy

1H Global sales / y-o-y growth N/A

Sitagliptin Dapagliflozin Canagliflozin Exenatide

741 485 587 233

24 24 26 24

On/not on an OHA Drug-naiveDrug-naïve or

AHA monotherapyTreat with diet and

exercise

US$1.7bn / -5.3% US$1.1bn / +46% US$286mn / -23% US$55mn / -8%

Placebo Effect in Chinese Trials

Study 1: The difference of HbA1c in the placebo arm between trials conducted in China and outside China is

-0.273 % (95 % CI [-0.42 %, -0.13 %], p-value is less than 0.001).

Study 2: In term of HbA1c change, treatment with placebo led to a significant HbA1c reduction from baseline

(WMD, 0.33%; 95% CI: -0.41% to -0.25%).(0.27)

(0.33)

Study 1 Study 2

(0.99)

(0.59)

(1.3)

(0.8)

(0.3)

0.2

Sitagliptin Placebo

Dorzagliatin Improved β-cell Function and Decreased Insulin Resistance

55Source: R Wang, H Liu, L Chen, Y Duan, Q Chen, S Xi J. Diabetes Res 2017

Type 2 Diabetes Rat Pancreas Type 2 Diabetes Rat Liver

Hua conducted several non-clinical studies in rats, mice and dogs. It showed that Dorzagliatin rescued glucose sensor

function in pancreas and liver, and it improved glucose and insulin sensitivity

Study results showed that number of insulin-immunopositive cells in pancreas and GK-immunopositive cells in liver

increased significantly after the administration of low-dose and high-dose Dorzagliatin

0

15

30

45

60

75

90


Nu

mb

er

of

Ins

uli

n-

Imm

un

op

os

itiv

e

Ce

lls

(b)

0

20

40

60

80

100


Nu

mb

er

of

GK

-Im

mu

no

po

sit

ive

C

ell

s (

%)

(b)

Control

HMS-L HMS-H

Diabetic Control

HMS-L HMS-H

Diabetic


Profile Compound Developer Clinical Stage Commentary

Chemical

Structure

Full GKA (β > 1)

Dorzagliatin Phase IIIOnly GKA to have advanced to Phase III

RO4389620Generated large amounts of unexpected human metabolites

AMG 151 / ARRY-403

High incidences of hypoglycemia and elevated serum triglycerides

MK-0941

Lack of sustained glycemic efficacy, increased incidence of hypoglycemia and elevations in triglycerides and blood pressure

Partial GKA(β < 1)

AZD-1656Reduced Vmax of GK and demonstrated limited efficacies in Type 2 diabetics

PF-04937319Phase II completed in US / IND approved in

China

Liver Selective GKA

TTP399Sustained efficacy and safety through 24 week; less efficacious than sitagliptin

PF-04991532Reduced Vmax of GK and demonstrated limited efficacies in Type 2 diabetics

Only Hua has advanced GKA to Phase III clinical trials

Dorzagliatin is Designed to Overcome the Flaws Witnessed in the Past GKA Candidates

56

Dorzagliatin targets GK both in pancreas and liver

Dual acting with full activation properties fit the profiles of a therapeutic agent to modulate glucose homeostasis in Type 2

diabetes patients

Selective

Acting

on GK in Liver

Glucokinase

Activator

Dual Acting

on GK in

Pancreas and

Liver

NH

N

N

N

NN


Dorzagliatin Chemical Structure is Unique

57

Hua Dorzagliatin Roche RO4389620

Merck MK-0941 AstraZeneca AZD-1656

NH N

N

N

NN


Hypoglycemia can be Prevented by Maintaining nH Close to Native Form of GK Enzyme

58

GK

A E

C50(u

M)

Glucose (mM)

0 1 10 100

8

7

6

5

4

3

1

0

2

nH=1.5

nH=1.0

Vmax, S0.5 and nH

GKA: “A” can change the Vmax and S0.5 of GK

α measures the change of affinity to glucose by GKA

β measures the change of catalytic efficiency by GKA

n is Hill coefficient (nH)

GK

Acti

vit

y (

uM

/min

)

Glucose (mM)

16141210

86

20

4

18202224

0 5 10 15 20 25 30

0

0.1 uM

0.3 uM

1 uM

3 uM

10 uM

30 uMDecreasing α

Increasing β

[S]0.5

Vmax

Dorzagliatin Does Not Modulate nH of GK to UnityEnzyme Activity Predictive Model

GKA Alters GK Enzyme Kinetic Properties

Wild type GK has an nH of 1.7

Dorzagliatin at 10 uM maintains GK nH of 1.5

GKA change nH toward unity (nH = 1.0) will disrupt GK glucose

sensing function and cause hypoglycemia


Dorzagliatin has Desirable Enzyme Kinetics Profile

Source: Li Chen, American Diabetes Association (ADA) 79th Scientific Sessions, 7-11 June, 2019, San Francisco, USA

Conclusion

The increase of GK Vmax with a GKA is desirable for developing a therapeutic agent for the treatment of patients with type 2 diabetes who

suffered from a down regulation of GK expression.

The results suggest that large changes of nH over 20% at 10 uM GKA concentration compared with drug free state may lead to clinical

hypoglycemia as an indicator for setting the GSIR threshold below 4 mM glucose.

Dorzagliatin

Influence of GKAs on key parameters of GK enzymatic

kinetics.

Piragliatin PF-04937319

MK-0941 AZD1656


IGT

T2D_4T2D_1

Pre-Diabetes Early Stage Diabetes Late Stage Diabetes

T2D_5

ObesityT2D_6T2D_2 T2D_3

Subtype Predominate InfluentialFactor

T2D_1 Severe Impaired Glucose Tolerance

T2D_2 Impaired β-cellFunction

T2D_3

T2D_4

T2D_5

T2D_6

Severe Impaired β-cell Function

Impaired Glucose Tolerance with aging

Severe Insulin Resistance with obesity

Impaired β-cell Function and Severe insulinresistance

Type 2 Diabetes Patients Subtype Analysis: Unbiased Machine Learning for Future Personalized T2D Care

This study demonstrated a viability of subclassifications type 2 diabetes patients through hyperdimensional machine learning framework

Although the study is conducted in a limited T2D patient population compared with the clustering analysis reported previously, our results were

based on a much higher dimension of variables from our high quality clinical trial data.

Different subtypes have responded differently to dorzagliatin in HbA1c reduction, but all of them showed improved HOMA2-β and reduced

HOMA2-IR, which supports dorzagliatin in combination with other T2D medicines in a personalized T2D care

Our results also suggests that each T2D subtypes may represent a unique state in the disease progression

Source: Lingge Feng, American Diabetes Association (ADA) 79th Scientific Sessions, 7-11 June, 2019, San Francisco, USA


Combination Therapy Options:Fix Sensor, Remodel Homeostasis, Control Diabetes

SGLT-2

Metformin

PPAR

DPP-4

GLP-1

AGI

Insulin

Dorza

+

DorzaMet

T2D_CV

Endo-GLP-1

T2D Obesity

Prevention

T1D Severe

T2D NASH

Extended

Injectable

Prevention


Massive China Diabetes Market with Drug Naïve Patients

62

China has the largest diabetes population globally, with half undiagnosed

China Has the Largest Diabetes Population with c.125 million T2D …with Diagnosis Rate Lower than Global Average

Number of Type 2 Diabetes Patients and Diagnosis Rate, Expected to Grow Significantly

Million

106 109 113 117 120 126 127 131 135 138 142 146 149 153 157 160

43.9% 44.7% 45.3% 46.1% 47.7% 50.4% 53.4% 56.6% 60.1% 63.9% 67.9% 71.3% 74.3% 77.1% 79.7% 82.2%

2013 2014 2015 2016 2017 2018 2019E 2020E 2021E 2022E 2023E 2024E 2025E 2026E 2027E 2028E

Number of T2D Patients in China Diagnosis Rate

50.4%

77.6%

54.2%

China US Global

Geographic Distribution of Global T2D Patients, 2018

125.7 , 27.0%

31.4 , 6.8%

307.6 , 66.2%

China

US

RoW

China Diabetics:

Increase in aging

population

Unhealthy diet

Lack of physical

activity

With improvements in social healthcare insurance system, increased healthcare expenditures and healthcare awareness, and

rising penetration of medical examination, diagnosis rate in China is expected to rise from 50.4% in 2018 to 82.2% in 2028

Source: Frost & Sullivan

Diagnosis Rate , 2017


1

Note: 1 the data refers to the actual diagnosis rate in China in 2018

Strong Demand for Next Generation OAD from Physicians and Patients

63

US Anti-diabetics Drug Market Breakdown By Drug Categories


Global anti-diabetics drug market reached US$68.9 bn in 2017, and is expected to reach US$137.7 bn by 2028

New drug class with novel mechanism of action has been very well accepted by physicians and patients

Dorzagliatin is a new generation of novel drug with breakthrough potential

1995 2005 2017

Market Size: US$3.2 bn Market Size: US$16.1 bn Market Size: US$34.6 bn

Insulin68%

Biguanides

7%α-glucosidase

inhibitors

7%

Sulfonylureas

18%

Insulin48%

Biguanides

4%

α-glucosidase

inhibitors

6%

Sulfonylureas +

Glinides

13%

Thiazolidinediones

(TZD)

29%

Insulin54%

GLP-114%

Biguanides

1%

Sulfonylureas +

Glinides

2%SGLT-2

5%

DPP-4

24%


33.0 38.1 42.5 47.0 51.2 57.3 65.9 76.5 90.3 103.8 118.4 123.2 135.6 149.1 161.0 173.9

2013 2014 2015 2016 2017 2018 2019E 2020E 2021E 2022E 2023E 2024E 2025E 2026E 2027E 2028E

China Anti-diabetics Market Size

China Anti-Diabetes Market Has Significant Headroom for Growth

64

Innovative drug categories will be a key growth driver for China anti-diabetics market

Breakdown of China Anti-diabetics Market, 2018

China Anti-diabetics Market

Billion RMB with wholesale price level

Driven by rising income, improving affordability and emerging innovative anti-diabetes drugs, China anti-diabetics

market is expected to grow at 11.7% CAGR from 2018 to 2028

Billion RMB,

with wholesale

price level

+11.7%

Anti-diabetics in the China market are dominated by

traditional drugs. Sales revenue from newer emerging drug

categories like DPP-4, GLP-1 and SGLT-2 inhibitors are still

relatively small

With rising income, expansion of national medical insurance

system and growth of innovative anti-diabetes drugs, the

China anti-diabetes market is projected to grow significantly

from RMB57.3 billion in 2018 to RMB135.6 billion in 2025,

and RMB173.9 billion in 2028

RMB57.3 billion

Market


Insulin

46.0%

Biguanides

9.5%

DPP-4

3.0%

GLP-1

1.2% Others

8.8%

α-glucosidase

Inhibitor

17.2%

Sulfonylureas

7.8%

Glinides

4.3%

Glitazones

2.2%


Top 15 Anti-Diabetic Global Sales —1H2019

65

1,908 1,732 1,702 1,6541,408 1,372

1,111 1,063737 726 720 690 620 557 542

0

500

1,000

1,500

2,000

2,500

Tru

licity®

Jan

uvia

®*

Lan

tus®

*

Vic

toza

®*

Hum

alo

g®

Novo

Rap

id®

*

Jard

ian

ce

®*

Jan

um

et®

*

Leve

mir

®*

Fa

rxig

a®

*

Novo

Mix

®*

Tre

sib

a®

*

Hum

ulin

®*

Oze

mp

ic®

Ba

sa

gla

r®

Top 15 Anti-Diabetic Global Sales – By Sales Value

(in USD mn)

Top 15 Anti-Diabetic Global Sales – By Sales Growth

(Y-o-Y comparison against 1H2018)

1300%

129%

85%

47% 47% 46% 46%31% 27% 25%

14% 7% 3% 3% 2%0%

50%

100%

150%

200%

250%

Oze

mp

ic®

Fia

sp®

So

liqu

a®

Ba

sa

gla

r®

Ryzo

deg

®

Jard

ian

ce

®*

Xu

lto

phy®

Tru

licity®

Glu

co

pha

ge®

*

Tre

sib

a®

*

Fa

rxig

a®

*

Glu

co

bay®

*

Novo

Oth

er

Invo

ka

me

t®

To

uje

o®

OralNon-Insulin

InjectablesInsulinNote: * denote drugs sold in China.

557 75 56 542 70 1111 156 1908 464 690 726 380 325 92 479 1H Sales

(in USD mn)

+31% +46% +14% +25% +1300% +47%Sales

Growth #2—#6 Drugs all declining #8—#9

declining


Top 15 Declining Anti-Diabetic Global Sales —1H2019

66

Top 15 Declining Anti-Diabetics Sales (Ranked by total sales)

(in USD mn)

Top 15 Declining Anti-Diabetes Sales (Ranked by sales decline)

(Y-o-Y comparison against 1H2018)

-23%

-17%-14%

-10%-8% -8% -6% -6% -5% -5% -5% -4% -3%

-1% 0%

-40%

-30%

-20%

-10%

0%

Invo

ka

na®

*

Lan

tus®

*

Leve

mir

®*

Hum

alo

g®

Hum

ulin

®*

Byett

a®

*

Insu

ma

n®

Jan

um

et®

*

Jan

uvia

®*

Vic

toza

®*

Ap

idra

®

Bydu

reon

®*

Novo

Rap

id®

*

Novo

Mix

®*

Am

ary

l®*

OralNon-Insulin

InjectablesInsulin

1,732 1,702 1,6541,408

1,3721,063

737 720 620

286 283 190 19255 48

0

500

1,000

1,500

2,000

2,500

Jan

uvia

®*

Lan

tus®

*

Vic

toza

®*

Hum

alo

g®

Novo

Rap

id®

*

Jan

um

et®

*

Leve

mir

®*

Novo

Mix

®*

Hum

ulin

®*

Invo

ka

na®

*

Bydu

reon

®*

Am

ary

l®*

Ap

idra

®

Byett

a®

*

Insu

ma

n®

Note: Soliqua is Non-Insulin Injectables.

-5.3% -16.7% -5% -10% -3% -5.8% -14% -1% -8% -23% -4% 0% -4.9% -8% -6% Sales

Decline


# of innovative drugs approved1

Local MNC

Source: CDE; EvaluatePharma; GBI; McKinsey analysis

Note: 1. Including both innovative chemical drugs and biologics.

2. As of October 25, 2019.

Innovations led by China NMPA accelerate the speed of new drug

launches and narrow the gap between China and global market

67

4

4045

28

3

9

6

2016

1

54

2018 2019YTD2

34

2017

7

41

Selected brands

approved in 2019

必特

Launch lag between China and global first launch

2016 2019

Launch lag

Years

Brand

(4)

Launch lag

Years

Brand

(28)

3.9 0.6

14.0 2.2

…

Average 8.4 Average 4.6

Average launch lag in 2019 still skewed by “legacy”

delays from prior years

…

8.8

6.9

8.8

1.6

1.8


New oral anti-diabetic drugs, especially DPP-4 and GLP-1 which entered the national medical insurance in 2017, are quickly growing market share.

68

Market Share of Oral Anti-diabetic Drugs

Source: Dorzagliatin Hospital Potential and SF Planning • March. 28, 2019 • © IQVIA 2019


China non-insulin anti-diabetes (NIAD) market sales value by class

69

Source: IQVIA analysis data on hospital market in China

Note: MAT 201909: 2018.10-2010.09


(mln RMB)

China NIAD value share by class (%)

70

Source: IQVIA analysis data on hospital market in China

Note: MAT 201909: 2018.10-2010.09


Comparison of Treatment Analysis of Type 2 Diabetes in China and the United States

71Source: Frost & Sullivan

Almost all T2D patients will need insulin as they gradually lose most of the β-cells

Medications comparison of type 2 diabetes in China and US are illustrated below. One major difference is that alpha-glucosidase inhibitors are still

used as first line drugs if metformin is not tolerated in China, whereas in US, alpha-glucosidase inhibitors are less popular.

In US, for most patients who need the greater efficacy of an injectable medication, a GLP-1 receptor agonist should be the first choice, ahead of

insulin. However, GLP-1 is not recommended in combination injectable therapy in China.

Monotherapy

Insulin secretagogues

α-glucosidase inhibitors

DPP-4 inhibitor TZDSGLT2

inhibitor

GLP-1 receptor agonist

Basal insulinOR OR OR OR OR OR

ADD

Basal insulinGLP-1

receptor agonist

Rapid-acting Insulin

Premixed Insulin

OROR AND/OR

Metformin +

Metformin is the first-line therapy in both China and US, while insulin secretagogues and alpha-glucosidase inhibitors may also used as first-line drug in China if metformin is not

tolerated.

MetforminInsulin secretagogues/

α-glucosidase inhibitors

OR

Dual and Triple Therapy Several options are available as second line treatment combined with metformin. SGLT-2 inhibitor, GLP-1 receptor agonist, basal insulin, insulin secretagogues, DPP-4 inhibitor and TZD

are recommended in both China the U.S. In China, insulin secretagogues including sulfonylureas and meglitinides are recommended while in the U.S, only sulfonylureas are

recommended.

Combination Injectable Therapy

Recommended only in US Recommended both in US and China Recommended only in China

GLP-1 receptor agonist is prior to insulin in US while in China, it is not recommended in combination injectable therapy.


Primary Anti-diabetics in China and United States

72Source: Currency exchange rate of USD1: RMB7.1815, USD1:DKK6.7529. Annual cost calculation assumes patients are on drug 360 days a year.

https://www.yaozh.com , https://www.drugs.com.Note： 1,2,3 Price of health insurance negotiation

Prices and Average Daily Cost of Top Anti-diabetics in China

Brand Name Generic Name CategoryStandard

Dosage

Drug Sales in

2018

(RMB bn)

Daily Cost

(RMB)

Estimated

Annual Cost

(RMB)

Glucobay® Acarboseα-glucosidase

Inhibitors3x0.1g/day 5.3 1.1 396

Lantus® Insulin Glargine Insulin 200U/week 4.5 17.7 6,372

Novomix® 30 Insulin Aspart 30 Insulin 200U/week 4.5 7.1 2,556

Ka Bo Ping® Acarboseα-glucosidase

Inhibitors3x0.1g/day 3.1 8.2 2,952

Chang Xiu Lin®Recombinant Insulin

GlargineInsulin 200U/week 2.7 14.0 5,040

Glucophage® Metformin Biguanides 2x0.5g/day 2.5 2.8 1,008

Novolin® 30RIsophane Protamine

Biosynthetic Human InsulinInsulin 200U/week 2.4 5.4 1,944

Novorapid® Insulin Aspart 30 Insulin 200U/week 1.9 7.2 2,592

Novonorm® Repaglinide Glinides 2x1mg/day 1.7 6.2 2,232

Amaryl® Glimepiride Sulfonylureas 2mg/day 1.4 4.6 1,656

Victoza® Liraglutide GLP-1 agonist1.2mg/day1.8mg/day

27.341.0

9,82814,760

Byetta® Exenatide GLP-1 agonist10μg/day20μg/day

43.353.3

15,58819,188

Januvia® Sitagliptin DPP-4 inhibitor 100mg/day 7.7 2,772

Invokana® Canagliflozin SGLT-2 100mg/day 4.1 1,476

Forxiga® Dapagliflozin SGLT-2 10mg/day 4.2 1,512

Insulin

+

New

Drug

with

Novel

MOA

Insulin

+

Older

General

OAD

+

Branded

Generic

New Injectable

Anti-diabetic

Reimbursable

Drugs in China

New Drug with

Novel MOA

Prices and Average Daily Cost of Top Anti-diabetics in US

Brand Name Generic Name Category Standard DosageDrug Sales in 2018

(USD bn)Daily Cost

(USD)Daily Cost

(RMB)

Estimated Annual Cost

(RMB)

Victoza® Liraglutide GLP-1 agonist1.2mg/day1.8mg/day

2.621.7

32.6

155.8

234.1

56,102

84,153

Januvia® Sitagliptin DPP-4 inhibitor 100mg/day 2.0 15.3 109.9 39,478

Trulicity® Dulaglutide GLP-1 agonist 1.5mg/week 2.5 28.6 205.4 73,941

Lantus® Insulin Glargine Insulin 200U/week 1.8 8.7 62.5 22,492

Humalog® Recombinant Insulin Lispro Insulin 200U/week 1.8 9.09 65.3 23,508

Novorapid® Insulin Aspart Insulin 200U/week 1.4 10.5 75.4 27,146

Levemir® Insulin Detemir Injection Insulin 200U/week 1.0 9.5 68.2 24,552

Jardiance® Empagliflozin SGLT-2 10mg/day 1.0 17.5 125.7 45,243

Janumet® Sitagliptin DPP-4 inhibitor 2*(50mg:1000mg)/day 0.8 16.0 114.9 41,364

Invokana® Canagliflozin SGLT-2 100mg/day 0.7 17.5 125.7 45,243

Farxiga® Dapagliflozin SGLT-2 10mg/day 0.6 17.5 125.3 45,114

1

2

3

4

5

6

7

8

9

10

11

1

2

3

4

5

6

7

8

10

9

11

12

13

14


2

1

3

Dorzagliatin Existing Patent Portfolio

Apr. 6, 2009

Dec. 20, 2013

Apr. 6, 2029

Dec. 20, 2033

Dec. 14, 2017

May 28 , 2019

Dec. 14, 2037

May 28, 2039

PCT/CN 2019/088861 other five applications

FDC

PCT/CN 2017/116209 Family (ZL 201711342429.9 and twodivs)

Formulation

PCT/EP 2013/077563 Family

Process

PCT/EP 2009/054067 Family

Compound


Version 002

version 2

Documents

Company Overview · Dorzagliatin Mono-therapy Trial for Drug Naïve T2D Patients (463 Patients) HMM0302: 24-week completed February 16, 2020 Dorzagliatin Metformin Add-on Therapy