REG - Sareum Holdings PLC - Nature article highlights role of TYK2 in Covid-19

Sareum HoldingsAnnouncement

14/12/2020 07:00

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20201214:nRSN4663Ia&default-theme=true

RNS Number : 4663I  Sareum Holdings PLC  14 December 2020

SAREUM HOLDINGS PLC

("Sareum" or "the Company")

TYK2 Identified as a Key Genetic Mechanism of Critical Illness in Covid-19 and
as an Important Potential Target for Therapy

Findings published in Nature support scientific rationale for Sareum's
SDC-1801 development programme in Covid-19 and its recent grant award from
UKRI

Cambridge, UK, 14 December 2020 - Sareum Holdings plc (AIM: SAR), the
specialist drug development company delivering targeted small molecule
therapeutics to improve the treatment of cancer and autoimmune diseases, is
pleased to note that a multi-centre analysis of DNA samples from patients with
severe forms of Covid-19, including symptoms caused by the over-active
inflammatory response ("cytokine storm"), has identified TYK2 as a key
causative genetic mechanism and a potential target for therapy.

This observation, which was published online as an Accelerated Article Preview
by Nature on 11 December 2020 (*Pairo-Castineira, E. et al.) is consistent
with the scientific rationale supporting Sareum's recent successful UK
Research & Innovation (UKRI) grant application for its proprietary
TYK2/JAK1 inhibitor, SDC-1801.

The funding from this grant (announced by the Company on 3 December 2020) will
be used to investigate the therapeutic potential of SDC-1801 in severe phase
Covid-19, in a six-month research project, with results expected around
mid-2021. This research will treat cells infected with the SARS-CoV-2 virus
with SDC-1801 to evaluate its potential to block the immune pathway that leads
to the cytokine storm in this life-threatening disease.

Sareum also intends to investigate if treatment with SDC-1801 in disease
models can re-establish protection against bacterial pneumonia following
SARS-CoV-2 infection.

Sareum's CSO, Dr John Reader, commented:

"The important findings of this extensive DNA analysis, which were highlighted
in this Nature Article Preview, provide strong support for our hypothesis that
TYK2 inhibition could be a significant contributor to the fight against the
life-threatening cytokine storm effects of severe Covid-19. We are very
pleased to have recently received a UKRI grant to test this hypothesis and
look forward to working closely with others in the field to evaluate the
potential of this new approach to bring a much-needed treatment option to
patients with severe Covid-19."

Reference

*Pairo-Castineira, E. et al. Genetic mechanisms of critical illness in
Covid-19. Nature https://doi.org/10.1038/s41586-020-03065-y
(https://doi.org/10.1038/s41586-020-03065-y) (2020).

This announcement contains inside information for the purposes of Article 7 of
Regulation 596/2014.

For further information, please contact:

Sareum Holdings plc

Tim Mitchell,
CEO
01223 497 700

Strand Hanson Limited (Nominated Adviser)

James Dance / Richard Tulloch
      020 7409 3494

Hybridan LLP (Nominated Broker)

Claire Noyce / John Beresford-Peirse
 020 3764 2341

Citigate Dewe Rogerson (Financial PR)

Mark Swallow/ David Dible
        020 7638 9571

About SDC-1801 and its potential to treat severe-phase Covid-19

SDC-1801 was designed by Sareum to be a potent and selective dual inhibitor of
tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1), which are part of the JAK
family of proteins. These are important in cytokine-mediated cell signalling,
which is a key component of the inflammatory response seen in autoimmune
diseases and potentially the cytokine-release syndrome (CRS) associated with
severe Covid-19. JAK inhibition, therefore, presents an attractive therapeutic
strategy for CRS, which is a common cause of adverse clinical outcomes in
Covid-19 and other viral infections.

SDC-1801 has demonstrated a potent anti-inflammatory effect in multiple
disease models and is currently in preclinical development with the potential
to become a new therapeutic targeting a wide range of inflammatory diseases,
such as psoriasis, systemic lupus erythematosus (SLE) and Crohn's disease. It
has demonstrated an encouraging safety profile in initial toxicity studies.

Covid-19 is caused by the virus SARS-CoV-2 and usually results in a mild
disease that resolves on its own. However, some patients develop a potentially
fatal severe disease due to inflammation arising from an overreaction of the
immune system, known as CRS or a 'cytokine storm', leading to Acute
Respiratory Distress Syndrome (ARDS), requiring intensive care. A major
inflammatory pathway mediated by TYK2/JAK1 - the Interferon Type 1 pathway
(Type 1 IFN) - is over-activated in severe Covid-19 patients and this pathway
may be able to be blocked by SDC-1801.

Recently, researchers have observed the similarity between severe Covid-19 and
the acute flares of lupus, an autoimmune disease characterised by
overproduction of Type I IFN(1). As Sareum reported in July 2020, SDC-1802, a
close analogue of SDC-1801, demonstrated encouraging results in a disease
model of lupus. The Company believes that SDC-1801 could potentially benefit
severe-phase Covid-19 patients by blocking signalling along this inflammatory
pathway and therefore reducing the 'cytokine storm'.

Furthermore, disease model studies have reported that specifically inhibiting
TYK2 activity restores the body's ability to protect against bacterial
pneumonia following influenza infection(2), suggesting that a TYK2 inhibitor,
such as SDC-1801, may have the same effect in Covid-19 patients. Serious
bacterial infections have been reported in up to 50% of critically ill
Covid-19 patients.

Positive results in its Covid-19 studies might lead to further opportunities
for the Company to investigate SDC-1801 in treating severe and
life-threatening inflammation that occurs as a result of other viral
infections.

References

(1) Woodruff M, et al. Critically ill SARS-CoV-2 patients display lupus-like
hallmarks of extrafollicular B cell activation. medRxiv  Preprint . (2020) May
3:2020.04.29.20083717. doi: 10.1101/2020.04.29.20083717. PMID: 32511635;
PMCID: PMC7276991.

(2) Berg J, et al. Tyk2 as a target for immune regulation in human
viral/bacterial pneumonia. Eur. Respir. J. 2017; 50: 1601953
https://doi.org/10.1183/13993003.01953-2016.

 

About Sareum

Sareum is a specialist drug development company delivering targeted small
molecule therapeutics to improve the treatment of cancer and autoimmune
diseases. The Company aims to generate value through licensing its candidates
to international pharmaceutical and biotechnology companies at the preclinical
or early clinical trials stage.

Sareum is advancing internal programmes focused on distinct dual tyrosine
kinase 2 (TYK2) / Janus kinase 1 (JAK1) inhibitors through preclinical
development as therapies for autoimmune diseases, including the "cytokine
storm" immune system overreaction to Covid-19 and other viral infections,
(SDC-1801) and cancer immunotherapy (SDC-1802).

The Company's preclinical FLT3+Aurora inhibitor programme targeting
haematological cancers is licensed to a China-based specialty pharma company.

Sareum also has an economic interest in SRA737, a clinical-stage oral,
selective Checkpoint kinase 1 (Chk1) inhibitor that targets cancer cell
replication and DNA damage repair mechanisms. Preliminary Phase 2 and
comprehensive preclinical data suggest SRA737 may have broad application in
combination with other oncology and immune-oncology drugs in genetically
defined patients.

SRA737 was discovered and initially developed by scientists at The Institute
of Cancer Research in collaboration with Sareum, and with funding from Sareum
and Cancer Research UK. SRA737 was licensed by CRT Pioneer Fund (CPF) to
Sierra Oncology Inc. Sierra is currently exploring options to obtain the
funding or support necessary to advance the future development of SRA737.

Sareum Holdings plc is listed on the AIM market of the London Stock Exchange,
trading under the ticker SAR. For further information, please visit the
Company's website at www.sareum.com (http://www.sareum.com) .

 

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  MSCEAXADFSPEFFA