Achilles Therapeutics · to “accredit investors” (“accredited investors”) as defined in Regulation D under the United States Securities Act of 1933, as amended (the “Securities

non-confidential © Achilles Therapeutics Ltd. 2019© Achilles Therapeutics Ltd. 2019

Achilles TherapeuticsPiper Jaffray Healthcare Conference

3rd December 2019


Important Notice

This information memorandum (the “Memorandum”) has been prepared by Achilles Therapeutics Limited (the “Company”) in connection with a possible equity

fundraising of the Company (the “Transaction”).

No representation or warranty, express or implied, as to the accuracy or completeness of the information contained in the Memorandum is made by the Company,

and no responsibility, obligation or liability (whether direct or indirect, in contract, tort or otherwise) is accepted by the Company or its affiliates, officers, employees,

agents or advisers in relation to the adequacy, accuracy or completeness of the information and opinions contained in, or enclosed with, the Memorandum or in any

other information made available in connection with the Transaction. In particular, no representation or warranty is given, and no responsibility or liability is

accepted, either as to the achievement or reasonableness of any future projections, forecasts, estimates or statements as to prospects or future returns contained or

referred to in the Memorandum or in relation to the basis or assumptions underlying such projections or forecasts. The Company does not accept any obligation to

revise or update any information contained in the Memorandum, regardless of whether that information is affected as a result of new information, future events or

otherwise. Nothing in this paragraph is intended to limit the liability of the Company for fraudulent misrepresentation.

Neither this document nor any part or copy of it may be taken or transmitted into the United States of America, or any state or other jurisdiction of the United

States (including its territories and possessions and the District of Columbia, the “United States”) or distributed, directly or indirectly, in the United States, other than

to “accredit investors” (“accredited investors”) as defined in Regulation D under the United States Securities Act of 1933, as amended (the “Securities Act”).

Any securities issued in connection with the Transaction will not be registered under the Securities Act and may not be offered or sold in or into the United States

unless the securities are registered under the Securities Act, or an exemption from the registration requirements of the Securities Act is available. No public offering

of the securities will be made in the United States. Any securities referred to herein have not been approved or disapproved by the United States Securities and

Exchange Commission, any state securities commission in the United States, or any other United States regulatory authority nor have any such authorities passed

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This document does not constitute or form part of any offer for sale or subscription of or solicitation or invitation of any offer to buy or subscribe for any securities,

including in the United States, nor shall it or any part of it form the basis of or be relied on in connection with any contract or commitment whatsoever. By accepting

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with the contents of this document. This document remains the property of the Company and on request this document and all material received from the

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The delivery of the Memorandum may be affected by the laws of the recipient’s relevant jurisdiction. It is the responsibility of recipients of this document, and not of

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and/or for the purposes of any further investigation of, and/or the entering into of any legally binding documentation in respect of, the Transaction, including

obtaining any requisite governmental or other consent and adhering to any other formality prescribed in such territories.

1

non-confidential © Achilles Therapeutics Ltd. 2019non-confidential © Achilles Therapeutics Ltd. 2019© Achilles Therapeutics Ltd. 2019

Agenda

02 Science Breakthrough potential in cancer therapeutics

03 ProgressDelivering clonal neoantigen T cells (cNeT) in the clinic

04 Clinical unmet need and opportunityProof-of-concept trials starting in NSCLC and melanoma

05 Summary

01 Introduction

2


A personalised T cell therapy guided by the DNA sequence of each

patients tumour

Achilles: A clinical stage company developing potentially transformative T cell therapies targeting multiple solid tumours

Achilles was founded in 2016 by Syncona (£28.25 M Series A) and completed a £100 M Series

B round in September 2019, led by RA Capital and joined by: Forbion, INVUS, Perceptive

Advisors and Redmile Group, amongst others

Based on pioneering research led by Prof. Charlie Swanton, Karl Peggs and Sergio Quezada

into tumour evolution, tumour microenvironment and the translation of personalised T cell

therapies

Successful clinical grade manufacturing with over 10 GMP runs completed from patient

material

CTA approved, patient material being processed and first patients to be dosed in Q1 2020

>70 staff based in Greater London with access to GMP licensed manufacturing facilities

3


Robert Coutts

Finance Director

Ed Samuel

SVP Manufacturing

Beverley Carr

CBO

Jane Robertson

CMO

• Over 13 years of commercial

experience in speciality and

advanced therapeutics

• Investment director in Nightstar

Tx, Blue Earth Dx and Achilles

• Involved in six worldwide

pharmaceutical product launches

• 18 years industry experience

spanning global pharma and

biotech

• Pre-clinical science leader

successfully translating research

into the clinic

• Established extensive IO project

pipelines at Roche and Medigene

• Over 12 years experience in the

fields of cell and gene therapy

• Expertise in process development

technology transfer and GMP

manufacturing

• Led European operations at

Orchard Therapeutics and

Cognate BioServices

Management team

• 20 years of business

development experience in

global pharma and biotech

• Led multiple transactions

including co-founding of Sitryx

Therapeutics and out-licensing of

Ofatumumab to Novartis

• Qualified accountant with over

13 years finance experience

across practice and industry

• Expertise in setup and

operationalisation of the finance

functions of multiple biotech

companies

• Certified oncologist with over 15

years drug development

experience

• Global Clinical development

leader of multiple studies

• Led Phase III development,

registration of AZ’s PARP

inhibitor Lynparza®

Iraj Ali

CEO

Markus Dangl

CSO

4


Board of Directors

• 25 years of business building and

Board level experience in over 15

companies

• Previously CEO of Ablynx, led the

landmark $4.8Bn sale to Sanofi

(2018)

Edwin Moses

Independent Chairman

• Leading venture investor and CEO

of Syncona (founding investor)

• Previously a Partner at MVM

leading their European operations

and involved in a number of

successful investments

• Principal on the Investment Team

at RA Capital Management

• Experienced public and private

market investor with in depth

knowledge of the solid tumour

oncology landscape

Martin Murphy

Investor DirectorMichael Giordano

Independent NED

• Previously SVP Development for

Immuno-Oncology at BMS

• At BMS led 12 product approvals

including Opdivo®, Yervoy®,

Empliciti® and Sprycel®

• Partner at Forbion

• Specialist in evaluation and

structuring of new investment

opportunities with a strong

focus on oncology

Karl Peggs

Founder Director

Derek DiRocco

Investor Director

Rogier Rooswinkel

Investor Director

• Clinical and Scientific Director of the

Sir Naim Dangoor Centre for Cellular

Immunotherapy (UCLH)

• Expert in the translation of T cell

therapies (led over clinical 20 cell

therapy trials)

• Pioneered the development of anti-

viral T cell therapies

• Published over 200 papers

5


Personalised solid tumour therapeutics:T cells targeting multiple clonal neoantigens (cNeT)

The most effective therapeutic targets for solid tumours

should be present on all cancer cells and absent from healthy

tissue – patient-specific clonal neoantigens

Targeting multiple patient-specific clonal neoantigens

minimises the possibility of evolved resistance and tumour escape

Achilles uses advanced manufacturing techniques

built on the established and clinically validated principles of tumour

infiltrating lymphocyte (TIL) therapy, combined with a unique ability to

identify patient-specific clonal neoantigens to generate potentially

transformational medicines

6


Achilles - key concepts

Exclusive access to the world’s most comprehensive solid

tumour data base, the TRACERx study, which has enrolled

over 600 NSCLC patients to date and has been used to

develop the PELEUSTM bioinformatics platform which can

be used to identify clonal neoantigens in a broad range of

tumours

A unique and

proprietary tool to

identify clonal

neoantigens

T cells recognise cancer antigens (through

their T cell receptor) and once the T cell

binds to the antigen, it becomes activated,

able to rapidly expand and then can seek and

destroy tumour cells

Clonal neoantigens are formed early in

evolution and are present on all cancer cells

7

T cell

Tumour

cell


VELOSTM manufacturing process: from tumour to treatment

8


Achilles technology represents the next wave of immuno-oncology approaches and is uniquely positioned to target clonal neoantigens

Checkpoint

Inhibition and ACT

Neoantigen Vaccines

Targeting Clonal

Neoantigens with T cells

(cNeT)

Achilles has a unique capability to detect and

target clonal neoantigens (based on TRACERx) and is further differentiated by

basing its therapeutic product on an advanced

version of a clinicallyvalidated TIL approach

9


Achilles’ IP and know-how

Designed to protect the use of T cells that specifically target clonal

neoantigens to treat cancer

Proprietary PELEUSTM bioinformatics platform for identifying clonal

neoantigens from patient samples

Proprietary VELOSTM advanced manufacturing process suitable for

commercial supply of personalised T cell therapeutics

Target

selection

Core use patent

applications

Cell

manufacturing

10


Corporate strategy

To develop personalised, clonal neoantigen T cell based therapeutics (cNeT) against a

range of commercially attractive solid tumour targets beginning with NSCLC and

melanoma

To rapidly generate clinical PoC data in the two lead indications and quickly develop a

pipeline targeting at least four additional indications

To continuously develop the VELOSTM manufacturing processes internally to support

clinical trials and to retain significant control of the commercial manufacturing process

To continuously develop the PELEUSTM bioinformatics platform to ensure it remains

the world-leading predictor of clonal neoantigens

To partner with pharma companies where they can bring additional resources and

specific indication expertise to fully exploit the cNeT platform

To commercialise some cNeT indications ourselves directly in certain geographies

11


The basic principle of Tumour Infiltrating Lymphocyte (TIL) therapy has delivered impressive clinical responses in multiple late stage settings

Overall Survival

Total mutational load and predicted neoantigen load

correlate with clinical benefit in TIL

- Lauss et al., Nature Comm, 2017

1 Forget et al., Clin. Can. Res. 2018

25% ORR in NSCLC in 12 patients (with 2 CRs and 1 PR)

– Moffitt Investigator Sponsored Study update at SITC Nov

2019

44% ORR in cervical cancer (3 times better than Keytruda), in

27 patients with 2.6 prior lines of therapy

– IOVANCE ASCO abstract May 2019

38% ORR in melanoma (with 2 CRs) and durable

responses (PFS 7.4 months). 55 patients,

3 lines of prior therapy and all PD-1 refractory.

– IOVANCE ASCO abstract May 2019

Durable tumour control (>35 months) in progressing

cholangiocarcinoma patient

- Tran et al., Science, 2014

Survival in response to TIL therapyProspective study in Metastatic Melanoma

74 patients, MD Anderson (2018)1

TIL has demonstrated profound efficacy

in multiple solid tumour settings

12


Despite impressive results, opportunities exist for improvement of first generation TIL therapy

1 Gattinoni et al. (2005) J Clin Invest

2 Lauss et al., (2017) Nature Comm

3 Snyder et al., (2014) NEJM13

TIL

• Non-specific expansion of all T cells with no control over which antigens are targeted

cNeT

• Modern proprietary process designed with scale-up and competitive COGS in mind

• TIL manufacturing process was developed in the 1980s in an academic setting

• Very high (non-physiological) levels of IL-2, which have been shown to result in more differentiated (or exhausted) T cells with reduced anti-tumour activity1

• cNeT process selectively targets neoantigens, which has been shown to correlate with the efficacy of TIL2 (and checkpoint inhibitors3)

• Natural dendritic cell driven T cell expansion (low IL-2)


Harnessing the power of Adoptive Cell Therapy (ACT) by targeting clonal neoantigens

• Patient specific clonal

neoantigens bind to T cell

receptors to dramatically

stimulate T cell expansion

• Antigen stimulation results in

the production of highly

specific and naturally active T

cells

• No gene editing is involved -

the approach is based on the

use of natural T cells

Identification of clonal

neoantigens enables the next

generation of TIL therapy

cNeT 2019

1 Porter et al., N Engl J Med, 2011 2 Rosenberg et al., N Engl J Med, 1988

TIL 19882

CAR-T20111

14


We have built PELEUS which is a bioinformatics tool that allows exquisite identification of clonal neoantigens

• The PELEUSTM platform has been trained on data obtained from TRACERx

• TRACERx is the largest ever longitudinal study of tumour evolution in lung cancer;

running over five years (started April 2014)

• Network of 15 NHS clinical sites will deliver 850 patients with harmonised

therapeutic protocols – £14M funding provided by Cancer Research UK (CRUK)

• Most extensive and highest quality bioinformatics data set of its kind globally (more

than 3X larger than the largest publicly available comparator, TCGA)

• Deep whole-exome sequencing across multi-region and multi-time point patient data

• The gold standard for neoantigen and clonality assessment

• Unparalleled source of patient material for process development

• 30,000 biological samples collected to date

• Achilles’ proprietary bioinformatics platform, PELEUS, has been developed

and trained using exclusive commercial access to the TRACERx data

• Know-how from TRACERx can be applied across multiple solid tumours

15

non-confidential © Achilles Therapeutics Ltd. 2019non-confidential © Achilles Therapeutics Ltd. 2019

Manufacturing reduced to practice

• Produced clinical doses of >100 million cNeT cells

• Product contains both cytotoxic (CD8+) and helper T cells (CD4+) which

can directly target tumour cells1-3 and are critical for durable responses4-5

Superior Potency

• In response to clonal neoantigens, cNeT cells secrete significantly higher

amounts (>5X) of effector cytokines compared to TILs6

• Compared to TILs, cNeT have a less exhausted phenotype which should

enable greater in vivo proliferation and improved anti-tumour activity7-8

A patient specific product

• The cNeT product contains personalised multiple clonally reactive T cell

populations to reduce the risk of relapse through tumour escape

Key achievements so far in cNeT production

161. Quezda et al., J Exp Med 2009; 2. Tran et al., Science, 2014; 3. Hunder et al., N Engl J Med, 2008; 4. Church et. al., Eur J Immunol,

2014; 5. Antony et al., J Immunol, 2005; 6. Achilles unbuplished data 7. Peggs et al., 2008; 8. Gattinoni et al., J Clin Invest, 2005


Achilles has successfully carried out 10 GMP manufacturing runs with patient samples

Access to multiple

different tumour

indications

Ethical approval for use of

tumour and blood for

process development and

GMP manufacturing

Tissue Collection Study (TBL)

Procurement of tissue and blood

from cancer patients

Prior to the start of its clinical trials, Achilles procured, manufactured and characterised 10

patient samples to GMP standard to help de-risk delivery of the clinical studies

Highly engaged patients

and clinicians at multiple

sites trained to procure

material and dose cNeT

17


cNeT demonstrate improved activity compared to TIL

cNeT process has been shown to produce both CD4+ and CD8+ T cell populations.

There is a strong body of pre-clinical data which shows CD4+ and CD8+ T cells

work in concert to deliver potent and durable responses1-3

TIL cNeT

T I L c N e T

0

2 0

4 0

6 0

8 0

1 0 0

%

re

ac

ti

vi

ty

C D 8 + R e s p o n s e

T I L c N e T

0

2 0

4 0

6 0

8 0

1 0 0

%

re

ac

ti

vi

ty

C D 4 + R e s p o n s e

1. Hunder et. a; (2008) NEJM; 2. Church et. al. (2014) Eur J

Immunol; 3. Antony et al. (2005) J Immunol18


Achilles is developing a commercial manufacturing capability

• Achilles GMP manufacturing footprint at

Royal Free Hospital (~50 doses/ year) will

be significantly expanded with two

additional facilities coming on-line:

• Rented capacity at the Cell Therapy

Catapult, Stevenage (UK), (H1 2021),

capacity ~200 doses/ year

• Achilles’ own fully controlled large scale

modular facility (H2 2022) - location to be

confirmed, capacity ~1000 doses/ year

Building a world-class

manufacturing footprint

• The Achilles’ VELOSTM process has been

designed in-house to be fit for commercial

use (not transferred from academia)

• Focused on the development of an end-to-

end closed process to reduce cost and

increase scale

• Manufacturing capacity already established

for delivery of FiH clinical trials

19


Achilles has opened two clinical trials in 2019

CHIRON

Advanced Non-Small Cell Lung

Cancer (Stage III-Stage IV)

4Q2019 – 4Q2021

THETIS

Recurrent or metastatic

malignant melanoma

4Q2019 – 4Q2021

• 40 patients with advanced

unresectable or metastatic NSCLC

• Never-smokers and EGFR/ALK/Ros-1

mutations excluded

• cNeT monotherapy (and future option

for combination with PD-1/PD-L1

inhibitor)

• 8 UK sites initially, expanding to EU

and US

• 20 patients with metastatic or

recurrent melanoma

• Acral, uveal and mucosal

melanoma excluded

• cNeT monotherapy

• 4 UK sites initially, expanding to

EU and US

20


Clinical objectives

Primary:

To assess the safety and tolerability of cNeT therapy

Secondary:

To evaluate the clinical efficacy of cNeT using RECIST 1.11 and imRECIST2

Exploratory:

• To evaluate the persistence, phenotype and functionality of cNeT cells and explore

correlation with clinical outcome

• To evaluate potential biomarkers of clinical activity

• To evaluate the utility of a bespoke plasma circulating tumour (ctDNA) assay

1. Eisenhauer et al., Eur J Cancer, 2009

2. Hodi et al., JCO, 2018 21


Significant opportunity for cNeT beyond lead indications

Lead indications

Potential follow-on indications

NSCLC Melanoma

Head

and Neck

Triple

Negative

Breast

Bladder Renal

• Indication selection driven by

medical unmet need, commercial

opportunity and suitability of cNeT

approach

• Pipeline of up to four follow-on

indications to potentially enter the

clinic by 2022, with a further eight

indications under consideration

• Highly engaged clinical partners

facilitate access to a wide range of

patient material through our Tissue

Collection Protocol (TBL)

22


Achilles Therapeutics: 2019-2022 potential key milestones

Q1 2020

First patient

dosed in UK

H2 2020

Interim-efficacy

read-out in NSCLC

and melanoma

H2 2020

Initial selection

of follow-on

indication(s)

Occupy new

Company HQ

in London

Q4 2021

Full clinical read-out

NSCLC and melanoma

(60 patients)

Q4 2019

File IND

H1 2021

Manufacturing

facility on-line

(Cell Therapy

Catapult)

H1 2022

Open registration

study

(NSCLC/melanoma)

Q4 2021

Open Ph I/II for

follow-on indications

2020 2021 20222019

H2 2022

Manufacturing

facility on-line (large

scale modular facility)

23


Achilles - Building a novel pipeline of solid tumour therapeutics at the cutting edge of precision medicine

World class scientific founders, investors and Board, who together with a highly

committed and ambitious management team are bringing potentially

breakthrough T cell therapies to the field of cancer therapy

Rapid generation of clinical data with interim read out from first two indications in

H2 2020 and full read-out by H2 2021

Pipeline of up to four additional indications to enter the clinic by 2022 with

another eight solid tumour targets under consideration

Manufacturing process has been designed for industrial use with >1000 doses of

capacity expected on-line by H2 2022

Opportunity for strategic engagement with a very select group of pharma parties

Combining science at the cutting edge of cancer genomics with a clinically

validated TIL cell therapy approach to deliver a truly personalised medicine which

could revolutionise areas of cancer treatment

24

Documents

Achilles Therapeutics · to “accredit investors” (“accredited investors”) as defined in Regulation D under the United States Securities Act of 1933, as amended (the “Securities