– Abstracts highlight pipeline programmes in
precision oncology, including novel LSD1 inhibitor –
– Further detail on A2A programme, including
novel biomarker for patient selection to be presented –
Exscientia plc (Nasdaq: EXAI) today announced that four
abstracts have been accepted for poster presentation at the
upcoming American Association for Cancer Research (AACR) Annual
Meeting 2023, being held April 14-19, 2023, at the Orange County
Convention Center in Orlando, FL. These abstracts highlight the
components of Exscientia's approach to precision discovery, design
and personalised medicine as well as planned innovation in the
clinic.
“The clinical and preclinical data showcased at AACR further
validate Exscientia's functional precision medicine platform and
translational research capabilities,” said Andrew Hopkins, D.Phil,
founder and Chief Executive Officer of Exscientia. “These new data
demonstrate the potential of integrating outstanding science with
cutting-edge AI, to efficiently identify novel targets with the
potential for increased probability of clinical success. We also
believe that our platform can be used to predict outcomes that help
identify cancer patients with high unmet need who may benefit most
from treatment. We look forward to advancing these programmes and
expanding our pipeline with the goal of developing
precision-designed, truly personalised medicines for patients
around the world.”
Abstracts Accepted for Poster Presentation:
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
Next generation precision cancer medicine mandates a deep
understanding of the disease milieu and drug function to create
complex patient selection biomarkers, more than single mutations.
To enrich for patients who will most likely respond to EXS21546
(‘546), Exscientia's clinical stage A2AR-selective antagonist
targeting the adenosine pathway, Exscientia researchers leveraged a
combination of single cell functional and transcriptomics from
complex primary patient samples to identify an adenosine-induced
immunosuppression biomarker signature (adenosine burden score or
ABS). The ABS correlates with checkpoint inhibitor (CI) response
prediction to potentially predict patients likely to benefit from
combined A2AR antagonism and CI. Here, researchers show that the
adenosine burden, as monitored by ABS, is reduced following
antagonism of A2AR with ‘546, which in turn restores CI response
potential. The ABS is being confirmed retrospectively in the
ongoing IGNITE Phase 1/2 clinical study of ‘546 in combination with
a PD-1 inhibitor in relapsed/refractory renal cell carcinoma (RCC)
and non-small cell lung cancer (NSCLC).
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
LSD1 is an epigenetic target with critical roles in oncology,
notably demethylating histones and other proteins, thereby
suppressing the expression of genes required for cellular
differentiation. Historically, LSD1 inhibitors in development have
been unable to achieve the combination of appropriate
pharmacokinetics, good brain penetrance and a reversible mechanism
of action. By leveraging generative design algorithms and active
learning, Exscientia designed a highly differentiated LSD1
inhibitor, EXS74539 (‘539). ‘539 is a potent, selective and
reversible brain-penetrant molecule, combining the potential to
treat tumours and metastases in the brain with potential clinical
safety benefits through reversible inhibition of LSD1. ‘539 is
currently in IND-enabling studies as a potential treatment across
oncology and haematology. Preclinical data has shown that ‘539 has
potent anti-proliferative activity in in vitro models of small cell
lung cancer (SCLC), with anti-tumour activity observed in selected
SCLC xenograft tumour-bearing mice.
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: Tuesday, April 18 / 1:30 PM -
5:00 PM EDT
Mapping and interpreting single cell functional and multi-omics
data at baseline and after perturbation of complex primary model
systems reveals a previously unexplored convergent putative target
landscape that Exscientia is further validating as potential
next-generation anticancer nodes. The high unmet medical need in
indications such as high grade serous ovarian cancer (HGSOC) drives
a requirement for innovation to uncover novel targets. Standard
target discovery processes that often heavily rely upfront on
outgrown cell line models with well-averaged readouts have hindered
approval rates for drugs entering trials. This study highlights
ongoing work using Exscientia's precision medicine platform in
combination with proprietary methodology for multi-omics and
multi-modal dataset mapping which could have the potential to
improve patient outcomes by uncovering clinical relevance at the
target discovery stage. Here, researchers report a novel way of
uncovering several high confidence convergent putative targets,
seemingly overlooked in cell line studies. By mechanistically
characterising one such functional sensitivity node,
ALK/FAK1/IGF1R, the study reveals tumour necrosis factor (TNF) via
the nuclear factor kappa B (NFкB) pathway as a promising focus area
for HGSOC via the evaluation of malignant pleural effusion and
ascites from patients with late stage ovarian cancer.
Title: Data from first-in-human study of EXS21546, an A2A
receptor antagonist, now progressing into Phase 1 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
Pharmacokinetics, pharmacodynamics, safety and tolerability of
EXS21546 were confirmed in a healthy volunteer study, allowing
selection of a starting dose for the ongoing IGNITE Phase 1/2 study
in combination with a PD-1 inhibitor in relapsed/refractory RCC
and NSCLC. The IGNITE trial design was based on extensive
simulations to enable the most efficient continuous reassessment
method settings, and will allow further verification of the patient
enrichment biomarker strategy (adenosine burden score or ABS).
About Exscientia
Exscientia is an AI-driven pharmatech 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,
pre-clinical studies and clinical trials of Exscientia’s product
candidates. 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 pre-clinical 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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