Arbutus Biopharma : Update on AB-729 and AB-836, an siRNA and capsid inhibitor currently in development for the treatment of chronic hepatitis B infection

Update on AB-729 and AB-836, an siRNA and capsid inhibitor currently in development for the treatment of chronic hepatitis B infection

Dr. Gaston Picchio, Chief Development Officer

Singapore HBV Cure Meeting

June 1, 2022

www.arbutusbio.com

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Broad Pipeline

HBV

COVID-19

RNAi Therapeutic

AB-729

Capsid Inhibitor (oral)	AB-836
PD-L1 Inhibitor (oral)	AB-101
RNA destabilizer (oral)	AB-161

Mpro small molecule

Nsp12 viral polymerase

Lead Optimization

IND Enabling

Phase 1

Phase 2

Phase 3

Marketed

AB-729-001single-ascending dose / multiple-ascending dose

AB-729-201 Combo trial (AB-729 + Peg-IFNa-2a + NA)

Combo trial (AB-729 + core inhibitor + NA)

AB-729-202 Combo trial (AB-729 + vaccine + NA )*

AB-836-001single-ascending dose / multiple-ascending dose

*Clinical trial expected to initiate in 1H 2022

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www.arbutusbio.com	NA: Nucleoside Analogue

3-Pronged Approach to Therapeutic Success

Suppress HBV DNA

Reduce viral antigens

Boost host immune response

Therapeutic success will

require a combination of agents with

complementary MOAs

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1	Suppress	2	Reduce
	Viral DNA		Viral Antigens
Block Replication	Block HBsAg
▪	NA	▪	RNAi
▪	Capsid Inhibitor	▪	RNA Destabilizer

• RNAi
• RNA Destabilizer

Reduce cccDNA Pool

• Capsid Inhibitor

Leading to an

HBV CURE

Block HBsAg

• RNAi
• RNA Destabilizer

Immuno-modulation

• PD-L1Inhibitor
• Interferon
• Therapeutic vaccines

Boost/Reawaken

Host Immune

3 Response

MOA: Mechanism of Action | NA: Nucleoside Analogue | HBsAg: HBV Surface Antigen

3

AB-729

RNAi

Therapeutic

Proprietary GalNAc-conjugate delivery technology provides

liver targeting and enables

subcutaneous dosing

GalNAc Linker

n

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Single trigger RNAi agent targeting all HBV transcripts

Inhibits HBV replication and lowers all HBV antigens

Pan-genotypic activity across HBV genotypes

Demonstrated complementarity with capsid inhibitors

Actively targets the liver

Active against cccDNA derived and integrated HBsAg transcripts

Clean profile in long term preclinical safety studies

HBx

sAg

sAg

Polymerase, Core Ag, eAg, pgRNA

4

AB-729-001 Phase 1a/1b Clinical Trial

Part 1 & 2: Single-ascending dose

AB-729 monotherapy (90mg single-dose) resulted in robust HBsAg and HBV DNA declines in

HBV DNA+ patients

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Part 3: Multiple Doses In cHBV Patients - Ongoing

1. 60mg Q4W
   HBV DNA-
2. 60mg Q8W

HBV DNA-

1. 90mg Q8W + TDF HBV DNA+

1. 90mg Q8W

HBV DNA-

1. 90mg Q12W
   HBV DNA-

1. 90mg Q8W HBV DNA-,

HBeAg+ only

HBV: Hepatitis B Virus | TDF: tenofovir disoproxil fumarate | cHBV: chronic HBV`

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