E therapeutics : Annual Report for the year ended 31 January 2023

Computing the future

of medicineTM

e-therapeutics plc

Annual report and accounts 2023

We integrate computational power and biology to discover life-transforming RNAi medicines.

Vision

Solve human disease through computation

Mission

Integrating computational power and biological data to discover life-transforming RNAi medicines

Purpose

Build an in-house pipeline of more effective medicines at a greater speed and significantly reduced costs compared to industry standards

Contents

Strategic report

1. Highlights
2. Overview
3. Investment case
4. Chair's statement

1. CEO's statement

1. CFO's review

1. Management Q&A

1. Strategic summary

1. Our strategy

1. Therapeutic pipeline

1. Business model
2. Stakeholder engagement

1. Environmental, social and governance
2. Risk management

Corporate governance

1. Governance
2. Board of directors
3. Scientific advisory board
4. Executive team

1. Corporate governance statement

1. Audit committee report
2. Remuneration committee report

1. Remuneration policy

1. Statement of remuneration

1. Directors' report

1. Directors' responsibilities statement

Financial statements

57 Independent auditors report

1. Income statement and statement of comprehensive income
2. Statement of changes in equity
3. Statement of financial position
4. Statement of cash flow
5. Notes to the financial statements

Annual General Meeting

1. Notice of Annual General Meeting

1. Explanatory notes to the resolutions

Advisors - see Inside Back Cover

To view our website visit: www.etherapeutics.co.uk

HIGHLIGHTS

Operational highlights

Pipeline

• RNAi strategy delivering a rapidly growing in-house pipeline of early first-in-class candidates, against target genes discovered using our HepNetTM computational platform. Comprehensive in vivo proof-of-concept data packages being generated.
• Active across a variety of areas of high unmet medical need, including cardiovascular disease, non-alcoholic steatohepatitis (NASH) and haematology. Investing in the cardiometabolic space as a key focus area.

Data

• Expansion of world's most comprehensive knowledge base of hepatocyte-centric biology to capture and model complex biological processes in the liver and tissues influenced by the liver, completing proprietary curation of
  100s of data sources.
• Increased integration of HepNetTM functionality and continued validation of our tools, in particular our hepatocyte-specific knowledge graph and proprietary target identification approaches.
• Mapping of human genetic validation of potential targets completed for more informed target triage.

Computation

• Integration of large language models (LLMs), such as OpenAI's GPT model, to radically enhance computational capabilities and transform HepNetTM into a dynamic knowledge resource.
• Expansion of artificial intelligence (AI) approaches that learn from experimental data deployed into siRNA (short interfering RNA) drug design.

IP

• Sustained intellectual property (IP) activity with patent applications filed on eight further inventions arising from the Company's proprietary GalNAc-siRNA technology, GalOmicTM.

Partners

• New collaboration with iTeos Therapeutics in immuno- oncology announced on 5 April 2022. Several milestone payments received since, in addition to upfront consideration, following the successful identification of potential targets and small molecule compounds.
• Successful completion of Galapagos NV collaboration in idiopathic pulmonary fibrosis (IPF), with all near-term milestones achieved demonstrating our ability to effectively identify potential therapeutic strategies and targets.

Post Period Highlights

• Filing of four new patent applications to protect innovation around novel gene targets, and associated disease relevant biology as well as proprietary siRNA stabilisation chemistries.
• Additional milestone achieved in collaboration with iTeos Therapeutics, resulting in an additional payment to the Company.

Strategic report

Financial highlights

Year-end cash and short-term

Revenue

Successful fundraise

investment bank deposits

£0.5m

£13.5m

£31.7m

2023

£0.5m

2023

£13.5m

2023

£31.7m

2022

£0.5m

2022

£22.5m

2022

£26.4m

2021

£0.3m

2021

£13.2m

2021

£12.80m

Operating loss

R&D spend

R&D tax credit receivable

£10.2m

£7.2m

£1.5m

2023

£10.2m

2023

£7.2m

2023

£1.5m

2022

£9.6m

2022

£6.1m

2022

£1.5m

2021

£4.5m

2021

£2.7m

2021

£0.8m

e-therapeutics plc  Annual report and accounts 2023

01

OVERVIEW

Better medicines faster

To materially increase the likelihood of successfully developing effective medicines, it is essential to overcome some fundamental obstacles in drug development:

Biology… there is a limited understanding of human biology across the biopharma industry

Druggability… conventional modalities are often challenged by an inability to design and develop a drug despite having identified a potential target

Efficiency… the R&D process is slow and expensive with poor methods of de-risking therapeutic hypotheses early

Novelty… new target discovery remains rare, with crowded competitive landscapes around the same established targets

At e-therapeutics, we have developed a powerful validated platform approach to help overcome these obstacles. By uniquely connecting the worlds of computation and RNA interference (RNAi) we can rapidly generate and prosecute novel potential drug candidates in a reproducible and translatable way.

Hepatocyte-focused
computational biology
platform to identify	RNAi platform
novel gene targets,
to generate
improve drug design
GalNac-siRNA
and increase
drug candidates
automation
that silence novel
	gene targets

Computational	RNAi Platform
Biology Platform

learn more on page 18

We use our HepNetTM computational biology platform to model disease complexity, test millions of therapeutic hypotheses in silico and then rank potential novel gene targets. Our GalOmicTM platform then allows us to generate RNAi medicines that specifically silence those genes.

The medicines we create are focused on silencing genes expressed in hepatocytes (liver cells) which perform key functions in biological processes vital for human health and represent important targets for a broad range of diseases.

02 e-therapeutics plc  Annual report and accounts 2023

INVESTMENT CASE

Our investment case

Strategic report

Unique market position

Our highly differentiated market position combining computational drug discovery with RNAi as a modality enables us to prosecute therapeutic hypotheses at some of the fastest speeds and lowest development costs currently available in the industry.

learn more on page 16

Computational biology pedigree

We have a long history in computationally modelling biology and enabling drug discovery. The expertise in this space and proprietary technology have been successfully translated to focus on hepatocytes and identifying novel targets.

learn more on page 18

Single-cell focus advantage

Hepatocyte-targeted interventions offer the opportunity to address a large variety of diseases and potentially access thousands of gene targets while also enabling a focus on highly specific datasets and tools that promote superior computational depth and accuracy.

learn more on page 16

Unrivalled hepatocyte knowledge

We have built the world's most comprehensive knowledge resource in hepatocyte-centric biology, creating a 'Google for hepatocytes' that models complex biological processes in the liver and in tissues influenced by the liver.

learn more on page 7

Proven RNAi platform

Benchmarking studies have demonstrated our GalOmicTM RNAi platform can effectively silence genes to industry leading standards. The platform is now being actively used to generate drug candidates that silence novel disease-associated genes identified by HepNetTM.

learn more on page 19

Expanding in-house pipeline

We are growing an in-house pipeline of compelling first-in- class and 'first-on-target' RNAi candidates to treat a wide range of complex liver-associated diseases that are being rapidly progressed towards the clinic.

learn more on page 20

High barrier to entry

The field of RNAi requires a high degree of technical expertise while operating in a highly active intellectual property landscape. We have deep expertise in the space across biology, chemistry, and IP.

learn more on page 16

Demonstrable speed of execution

In less than three years we have built and validated an entire proprietary RNAi platform approach, pivoted our computational biology platform to hepatocyte-focused target identification and generated a wealth of in-house experimental data.

learn more on page 7

e-therapeutics plc  Annual report and accounts 2023

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