Data Presented at AACR 2023 Highlights Exscientia’s Clinical and Preclinical Development
April 19 2023 - 9:00AM
Business Wire
- Includes recent advancements from precision
designed compounds -
- Functional personalised medicine platform
unveiling unique adenosine biomarker to enrich for patients more
likely to respond to treatment -
Exscientia plc (Nasdaq: EXAI) today announced four presentations
at the American Association for Cancer Research (AACR) Annual
Meeting 2023, being held from April 14-19, 2023 in Orlando, FL.
“We’re excited to further validate Exscientia’s end-to-end
approach of integrating outstanding science with cutting-edge
AI-driven precision medicine and translational research
capabilities,” said Andrew Hopkins, D.Phil, founder and Chief
Executive Officer of Exscientia. “The clinical and preclinical data
showcased at AACR demonstrate how our approaches help not only
efficiently design novel molecules, but also aim to differentiate
them through superior properties and targeting the right patients
to benefit from them. We look forward to continuing to develop our
personalised medicine candidates with the goal of providing
solutions to patients in need of effective treatment around the
world.”
Poster Presentations
Title: Identification of transcript adenosine fingerprint
to enrich for A2AR and PD-1 inhibition responders Session
Title: Biomarkers of Therapeutic Benefit 2 Abstract
Number: #2151 Date/Time: Monday, April 17 / 9:00 AM -
12:30 PM EDT
- In this poster, Exscientia reveals its internally and
preclinically developed adenosine burden score (ABS; first revealed
at the end of 2022) is based on B-cell biology and that EXS21546
(‘546), Exscientia’s selective clinical stage A2AR antagonist,
reverts effects of adenosine analogues ex vivo in patient tissue
samples and other complex models
- Leveraging proprietary data, it was determined that the ABS is
inversely correlated with PD-1 expression pathways as well as
published PD-1 enrichment scores. Analysis of public human and
mouse data confirms an enrichment of ABS-high samples are among
those less likely to respond to checkpoint inhibition
- Current modelling in complex human blood samples shows that
‘546 as well as an example dual A2AR and A2BR antagonist are both
highly correlated in reversing effects of adenosine analogue ex
vivo
Title: Characterizing antitumor responses to EXS74539, a
novel, reversible LSD1 inhibitor with potential in small-cell lung
cancer Session Title: Epigenetics Abstract Number:
#6290 Date/Time: Wednesday, April 19 / 9:00 AM - 12:30 PM
EDT
- Exscientia precision-designed EXS74539 (‘539), an LSD1
inhibitor with a differentiated profile combining reversibility and
brain penetrance, to optimally target LSD1 in future oncology and
haematology patient populations, including small-cell lung cancer
(SCLC)
- The reversible mechanism-of-action combined with a shorter
half-life may provide an opportunity to better manage on-target
dose-limiting thrombocytopenia observed with other LSD1 inhibitors
in development
- In vitro sensitivity analysis of small cell lung cancer (SCLC)
cell line models to ‘539 alone was shown to not sufficiently
predict in vivo response; researchers believe that predicting in
vivo tumour response to ‘539 is critical to ensuring optimal use of
the compound. Combining transcriptional and functional responses in
vitro, however, may overcome this
- Exscientia has identified genetic fingerprints which may
function as markers of ‘539 sensitivity, which are undergoing
characterisation and validation in human SCLC patient samples
Title: Discovering novel targetable pathways by combining
functional and multi-omic data from primary ovarian cancer samples
Session Title: Novel Targets and Pathways Abstract
Number: #4956 Date/Time: Sunday, April 16 / 1:30 PM -
5:00 PM EDT
- This poster highlights the use of data generated with
Exscientia’s precision medicine platform in combination with its
proprietary methodology for multi-omics and multi-modal dataset
mapping. By better understanding disease function, these tools
combined can be leveraged to improve patient outcomes by uncovering
clinically relevant targets at the discovery stage
- Data collected from disease-relevant patient samples including
single cell functional responses, transcriptomics, protein-protein
interactions and known drug-to-target interaction landscapes are
combined with the goal of understanding cancer targets in the
context of known biology, thereby understanding the target's
function and relevance early on in development, instead of relying
on single endpoints common in the industry
- By mapping single cell functional and multi-omics data at
baseline and after perturbation of a complex primary model system,
researchers uncovered the PI3K/AKT/mTOR pathway as a novel
anticancer node in high grade serous ovarian cancer (HGSOC). The
poster further defines tumour necrosis factor (TNF) induced
apoptosis function of the nuclear factor kappa B (NF-кB) pathway
via TRAIL (TNF-related apoptosis-inducing ligand) as a promising
focus area for HGSOC
Title: Data from first-in-human study of EXS21546, an A2A
receptor antagonist, now progressing into Phase 1/2 in RCC/NSCLC
Session Title: Phase I Clinical Trials in Progress
Abstract Number: #CT114 Date/Time: Monday, April 17 /
1:30 PM - 5:00 PM EDT
- ‘546 is the first AI-designed immuno-oncology candidate in the
clinic. Phase 1 objectives were achieved in a healthy volunteer
study, confirming pharmacokinetics, pharmacodynamics, safety, and
tolerability of ‘546, allowing selection of a starting dose for the
ongoing IGNITE Phase 1/2 study in combination with a PD-1
inhibitor in patients with relapsed/refractory renal cell carcinoma
(RCC) and non-small cell lung cancer (NSCLC)
- The poster highlights the IGNITE trial design, which is based
on extensive simulations to enable the most efficient continuous
reassessment method settings to predict and most accurately
evaluate the anti-tumoural effect of ‘546 in combination with
checkpoint inhibition as well as any dose limiting toxicity
- The IGNITE trial will also provide clinical data to support
Exscientia’s patient enrichment biomarker strategy, using the ABS
to identify patients with adenosine rich tumour microenvironments
who may benefit from treatment. The first patient is expected to be
enrolled in the first half of 2023
About Exscientia Exscientia is an AI-driven precision
medicine company committed to discovering, designing and developing
the best possible drugs in the fastest and most effective manner.
Exscientia developed the first-ever functional precision oncology
platform to successfully guide treatment selection and improve
patient outcomes in a prospective interventional clinical study, as
well as to progress AI-designed small molecules into the clinical
setting. Our internal pipeline is focused on leveraging our
precision medicine platform in oncology, while our partnered
pipeline broadens our approach to other therapeutic areas. By
pioneering a new approach to medicine creation, we believe the best
ideas of science can rapidly become the best medicines for
patients.
Visit us at https://www.exscientia.ai or follow us on Twitter
@exscientiaAI.
Exscientia Forward-Looking Statements This press release
contains forward-looking statements as that term is defined in the
Private Securities Litigation Reform Act of 1995, including with
respect to Exscientia’s plans to present at AACR, the progress of
discovery and development of candidate molecules, and the timing
and progress of, and data reported from, preclinical studies and
clinical trials of Exscientia’s product candidates, including with
respect to the dosing of the first patient in the Phase 1/2 IGNITE
trial. Any statement describing Exscientia’s goals, plans,
expectations, financial or other projections, intentions or beliefs
is a forward-looking statement and should be considered an at-risk
statement. Such statements are subject to a number of risks,
uncertainties and assumptions, including those related to:
initiation, scope and progress of Exscientia’s and its partners’
planned and ongoing preclinical studies and clinical trials and
ramifications for the cost thereof; clinical, scientific,
regulatory and technical developments; the process of discovering,
developing and commercialising product candidates that are safe and
effective for use as human therapeutics; and other factors. In
light of these risks and uncertainties, and other risks and
uncertainties that are described in the Risk Factors section and
other sections of Exscientia’s Annual Report on Form 20-F, filed
with the Securities and Exchange Commission (SEC) on March 23, 2022
(File No. 001-40850), and other filings that Exscientia makes with
the SEC from time to time (which are available at
https://www.sec.gov/), the events and circumstances discussed in
such forward-looking statements may not occur, and Exscientia’s
actual results could differ materially and adversely from those
anticipated or implied thereby. Although Exscientia’s
forward-looking statements reflect the good faith judgement of its
management, these statements are based only on facts and factors
currently known by the Company at the time of this press release.
As a result, you are cautioned not to rely on these forward-looking
statements.
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Investor Relations: Sara Sherman
investors@exscientia.ai
Media: Oliver Stohlmann media@exscientia.ai
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