Achilles Therapeutics · to “accredit investors” (“accredited investors”) as defined in...
Transcript of Achilles Therapeutics · to “accredit investors” (“accredited investors”) as defined in...
non-confidential © Achilles Therapeutics Ltd. 2019© Achilles Therapeutics Ltd. 2019
Achilles TherapeuticsPiper Jaffray Healthcare Conference
3rd December 2019
non-confidential © Achilles Therapeutics Ltd. 2019© Achilles Therapeutics Ltd. 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”).
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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
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otherwise. Nothing in this paragraph is intended to limit the liability of the Company for fraudulent misrepresentation.
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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
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non-confidential © Achilles Therapeutics Ltd. 2019© Achilles Therapeutics Ltd. 2019
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
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non-confidential © Achilles Therapeutics Ltd. 2019© Achilles Therapeutics Ltd. 2019
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
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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
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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
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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
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T cell
Tumour
cell
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VELOSTM manufacturing process: from tumour to treatment
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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
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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
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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
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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
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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)
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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
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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
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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
non-confidential © Achilles Therapeutics Ltd. 2019© Achilles Therapeutics Ltd. 2019
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
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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
non-confidential © Achilles Therapeutics Ltd. 2019© Achilles Therapeutics Ltd. 2019
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
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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
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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
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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)
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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)
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non-confidential © Achilles Therapeutics Ltd. 2019© Achilles Therapeutics Ltd. 2019
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
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