Exscientia Announces Expansion of its Precision Oncology Pipeline
March 14 2023 - 7:00AM
Business Wire
— Precision designed LSD1 and MALT1 inhibitors
currently progressing through IND-enabling studies —
— Both molecules demonstrate Exscientia’s
ability to overcome critical design challenges and identify high
quality drug candidates with potential increased probability of
success —
— Company on track to meet target of four
molecules in clinical development by 2024 —
— Watch video presentation reviewing both
compounds —
Exscientia plc (Nasdaq: EXAI) today announced two new
wholly-owned precision oncology development candidates, EXS74539
(‘539), an LSD1 inhibitor, and EXS73565 ('565), a MALT1 protease
inhibitor. These compounds have been precision designed to improve
the potential for patient benefit and solve complex design issues
that may limit the probability of success of other compounds in
development. IND-enabling studies are underway and the Company
expects to provide an update on clinical development plans
leveraging Exscientia's personalised medicine platform in the
second half of 2023.
Both molecules were funded through a 2019 collaboration with
Celgene, which was acquired by Bristol Myers Squibb, and each
molecule met the criteria for which BMS could exercise its option.
Bristol Myers Squibb's options to the candidates have now lapsed
and Exscientia maintains all worldwide rights to both compounds. In
2021, an agreement was signed to expand the collaboration to
include additional programmes in oncology and immunology. These
programmes are currently in active development.
“Building off of our success with the CDK7, A2A and PKC-theta
programmes, these candidates clearly show how our AI-driven
precision design platform can solve challenging target profiles in
a more efficient way than traditional drug discovery,” said
Professor Andrew Hopkins, D.Phil., founder and Chief Executive
Officer of Exscientia. “Both '539 and '565 met the primary
nonclinical design goals for potency, selectivity, dosing and
safety. In addition, these molecules also have the potential for
meaningful patient selection strategies to optimise clinical
design. We are excited about the promise these compounds hold in a
broad range of haematologic and solid tumours.”
First potent, selective, reversible and brain-penetrant LSD1
inhibitor: EXS74539 ('539) is a differentiated lysine
demethylase 1 (LSD1) inhibitor with potential in both haematology
and oncology. LSD1 demethylates histones play a critical role in
regulating the expression of genes which suppress differentiation
and drive the proliferation and survival of a number of tumour
types. To date, other LSD1 inhibitors in development have failed to
achieve the combination of appropriate pharmacokinetics, good brain
penetrance and a reversible mechanism of action. Exscientia's
candidate, '539, achieves a design objective of suitable CNS
penetration to target brain metastases, which are prevalent in
certain cancer subtypes. Additionally, in vivo studies of '539 have
shown favourable activity in small cell lung cancer (SCLC)
xenograft models, with dose dependent inhibition of tumour growth.
Studies have also shown a favourable absorption, distribution,
metabolism, and excretion (ADME) profile, with a shorter predicted
human half-life than some LSD1 inhibitors currently in clinical
trials. No safety concerns have been observed in preclinical
studies conducted to date. Exscientia will present data on the
discovery and development of '539 at an upcoming scientific
conference in the first half of 2023.
Potent and selective MALT1 protease inhibitor with potential
safety differentiation: EXS73565 ('565) is a mucosa-associated
lymphoid tissue lymphoma translocation protein 1 (MALT1) protease
inhibitor with potential applications in haematology. MALT1 is a
protease crucial for activation of the NF-κB pathway which supports
the uncontrolled proliferation of malignant T- and B-cells in
haematological cancers. Exscientia’s precision design approach was
able to optimise the safety profile for agents targeting MALT1
whilst also generating potency and selectivity. Scaffolds of other
MALT1 inhibitors in the clinic significantly inhibit UGT1A1, an
enzyme involved in the metabolism of bilirubin, often leading to
dose-limiting toxicities in the clinic. In vivo studies of '565
have shown anti-tumour activity in mouse models and favourable
pharmacokinetics both as monotherapy and in combination with
ibrutinib. Toxicology studies have shown that ‘565 has an
acceptable therapeutic index, with the ability to maintain high
levels of potency, selectivity and safety benchmarks while avoiding
meaningful inhibition of UGT1A1, which can lead to
hyperbilirubinemia.
“With three existing clinical programmes already in the
pipeline, we feel very confident we will meet our goal of four
clinical stage compounds in 2024,” said Prof. Hopkins. “Our vision
is to change the way drug design, discovery and development is
done, as we have shown in our first eight drug candidates. Over the
course of 2023, we expect to provide more details on these
programmes as well as on our broader internal and partnered
pipeline.”
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.
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 the progress of discovery and
development of candidate molecules, and the timing and progress of,
and data reported from, clinical trials of Exscientia’s product
candidates, and Exscientia’s expectations regarding the potential
benefit of any of its product candidates or number of clinical
stage candidates Exscientia expects to have by 2024. 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: the impact that
macroeconomic conditions and geopolitical events could have on the
Company’s business; the 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 the endeavour of building a business around such
product candidates. 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 judgment of its
management, these statements are based only on facts and factors
currently known by the Company. 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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