Exscientia to Present New Preclinical Data for AI-designed LSD1 and MALT1 Inhibitors at ENA 2024
09 Octobre 2024 - 1:00PM
Business Wire
Demonstrated combination potential for MALT1
and BTK inhibitors in models of B-cell malignancies
Data highlights efficacy of ‘539 in a
preclinical AML model, with limited impact on platelet levels
Identified PD biomarkers related to LSD1
inhibitor treatment
Exscientia plc (Nasdaq: EXAI) today announced three abstracts to
be presented at the 36th EORTC-NCI-AACR (ENA) Symposium 2024 from
October 23-25, in Barcelona, Spain.
“As our precision-designed LSD1 and MALT1 inhibitors continue to
progress towards the clinic, we are excited to share new
preclinical data from both programmes,” said David Hallett, Ph.D.,
interim Chief Executive Officer and Chief Scientific Officer of
Exscientia. “These posters, as well as an additional focus on our
assay development, highlight the potential of our platform to
design best-in-class molecules with improved properties. As our
state-of-the-art automation facility continues to ramp up in scale,
we look forward to further accelerating the design and development
of future molecules.”
The ENA posters will be available on the Exscientia website from
their time of presentation.
Poster Presentations Title: Combining
next-generation BTK and MALT1 inhibitors to enhance efficacy and
therapeutic utility in B-cell malignancies Session Title:
Combination therapies Catalog Number: 218 Poster Board
Number: PB206 Date/Time: Thursday, October 24 / 9:00
a.m. – 5:30 p.m. CEST
- EXS73565 (‘565) is a potent, selective allosteric MALT1
inhibitor designed to have an improved safety profile, with
clinical studies expected to start in early 2025
- Combining MALT1 inhibitors, such as ‘565, with BTK inhibitors
has the potential to provide enhanced efficacy in B-cell
malignancies, by greater inhibition of pathogenic nuclear
factor-kappa B (NF-kB) signalling and addressing BTK-resistance
mechanisms
- Exscientia researchers combined ‘565 with the BTK inhibitor
zanubrutinib and observed deeper, more durable efficacy responses
in xenograft models of B-cell malignancies, with long-lasting
tumour eradication seen for activated B-cell-like diffuse large
B-cell lymphoma (ABC-DLBCL)
- Studies also confirmed target pathway biology engagement, with
‘565 alone and in combination with zanubrutinib inhibiting NF-kB
target gene expression in in vivo models
- Overall, the selective profiles of ‘565 and zanubrutinib may
maximise the therapeutic index of MALT1 and BTK inhibition in
combination, providing scope for enhanced efficacy for patients
with B-cell malignancies
Title: In vivo pharmacokinetics, pharmacodynamics and
anti-tumour efficacy of EXS74539: A novel, reversible LSD1
inhibitor for acute myeloid leukaemia Session Title:
Epigenetic modulators (HDAC bromodomain modulators, EZH2)
Catalog Number: 250 Poster Board Number: PB238
Date/Time: Thursday, October 24 / 9:00 a.m. – 5:30 p.m.
CEST
- ‘539 is a novel, potent, selective and reversible LSD1
inhibitor, with a highly differentiated profile and designed to be
brain penetrant, expected to enter the clinic in early 2025
- The poster highlights that by combining ex vivo perturbation of
primary human acute myeloid lymphoma (AML) samples with ‘539 and
omics profiling, 12 potential pharmacodynamic (PD) biomarker gene
candidates were identified that correlate with LSD1 inhibitor
activity
- Upregulation of the identified biomarker gene candidates was
confirmed in an in vivo AML xenograft model post ‘539
treatment
- Treatment of the in vivo model with the reversible inhibitor
‘539 resulted in limited platelet level effects, highlighting how
‘539 was designed to maximise target engagement while limiting
thrombocytopenia
Title: Xcellomics: Powering rapid translation of HTS
outputs to AI-driven drug discovery programmes Session
Title: Functional genomics Catalog Number: 414 Poster
Board Number: PB402 Date/Time: Friday, October 25 / 9:00
a.m. – 3:00 p.m. CEST
- Xcellomics is a collaboration between Exscientia and The Centre
for Medicines Discovery at the University of Oxford, used to
rapidly translate the results of cell-based, high-throughput
screens into transformative oncology therapies
- The collaboration has successfully identified and validated
novel essential regulators of a key oncogenic pathway
- Automated assay development and chemical hit ID performed by
Exscientia rapidly pushed these novel therapeutic targets into drug
discovery programmes
About Exscientia
Exscientia is a technology-driven drug design and development
company, committed to creating more effective medicines for
patients, faster. Exscientia combines precision design with
integrated experimentation, aiming to invent and develop the best
possible drugs in the most efficient manner. Operating at the
interfaces of human ingenuity, artificial intelligence (AI),
automation and physical engineering, we pioneered the use of AI in
drug discovery as the first company to progress AI-designed small
molecules into a clinical setting. We have developed an internal
pipeline focused on oncology, while our partnered pipeline extends
to many other therapeutic areas. By leading this new approach to
drug creation, we believe we can change the underlying economics of
drug discovery and rapidly advance the best scientific ideas into
medicines for patients.
For more information visit us on www.exscientia.com or follow us
on LinkedIn @ex-scientia and X @exscientiaAI.
Forward-looking Statements This press release contains
certain forward-looking statements within the meaning of the “safe
harbor” provisions of the Private Securities Litigation Reform Act
of 1995. Words such as “anticipates,” “believes,” “expects,”
“intends,” and “projects” or similar expressions are intended to
identify forward-looking statements. All statements, other than
statements of historical facts, included in this press release are
forward-looking statements. These statements include, but are not
limited to, statements regarding the combination potential for
MALT1 and BTK inhibitors in models of B-cell malignancies, PD
biomarkers related to LSD1 inhibitor treatment and the benefits of
reversible LSD1 inhibition on platelets as well as the ability of
Exscientia’s technology to design compounds to create more
effective medicines for patients. Such statements are subject to a
number of risks, uncertainties and assumptions, including those
related to: the 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 development
and deployment of new technology and facilities; 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;
and the process of creating a combined company with Recursion
Pharmaceuticals and subsequent activities by any such combined
company. 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
21, 2024, 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. As
a result, investors are cautioned not to rely on these
forward-looking statements. Exscientia undertakes no obligation to
publicly update or revise any forward-looking statements, whether
as a result of new information, future events or otherwise, except
as may be required by law.
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Investor Relations: Sara Sherman investors@exscientia.ai
Media: David Keown media@exscientia.ai
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