Redx Pharma plc Preclinical data presented at cancer conference (2718G)
05 November 2018 - 6:00PM
UK Regulatory
TIDMREDX
RNS Number : 2718G
Redx Pharma plc
05 November 2018
REDX PHARMA PLC
("Redx" or "the Company")
Preclinical data evaluating RXC004 presented at the NCRI cancer
conference
Results demonstrate potential of RXC004 in genetically-defined
tumour types
Alderley Park, 5 November 2018. Redx (AIM: REDX), the drug
development company focused on cancer and fibrosis, is pleased to
announce the presentation of positive data from preclinical studies
evaluating RXC004 during a poster session, entitled 'Efficacy of
the Porcupine inhibitor RXC004 in genetically-defined tumour types'
today at the National Cancer Research Institute (NCRI) 2018 Cancer
Conference in Glasgow. RXC004 is a novel, oral, potent small
molecule Porcupine inhibitor, which targets the
Wnt/<BETA>-catenin pathway. It is expected to re-enter the
clinic in H1 2019 in a Phase 1/2a study in patients with advanced
malignancies.
The full abstract of the presentation can be found below.
Richard Armer, Chief Scientific Officer commented: "We are
delighted to showcase some of the fantastic science happening at
Redx. We are encouraged by the preclinical data presented at the
NCRI, which demonstrates the exquisite sensitivity of specific
genetically defined cancer models to our Porcupine inhibitor,
RXC004. The strength of these data highlight some of the broad and
multiple options available for the future development of this
programme as we look to re-enter the clinic in the first half of
2019."
NCRI 2018 Abstract
Background
Potent and selective porcupine (PORCN) inhibitor RXC004 is being
investigated in a Phase 1 clinical trial (NCT03447470). PORCN is a
membrane bound O-acyltransferase responsible for post-translational
modification of Wnt ligands, essential for Wnt secretion and
activity. Wnt pathway alterations, including RNF43 loss-of-function
mutations and RSPO fusions, result in increased levels of surface
Fzd receptors, increasing Wnt-ligand dependent signalling. These
alterations are implicated in colorectal, gastric, pancreatic and
biliary cancer. This work assesses the direct tumour targeting
effects of RXC004 in genetically selected cancer lines in vitro and
in vivo.
Method
RXC004 was evaluated in 2D and/or 3D in vitro proliferation
assays across a panel of colorectal and pancreatic cancer cell
lines. In parallel, cell cycle analysis was assessed using flow
cytometry. Downstream markers of target engagement for the Wnt
pathway, Axin2 and c-Myc, were analysed for mRNA expression using
qPCR. RXC004 was orally dosed for efficacy, PK and PD studies in
RNF43 mutant and RSPO fusion xenograft models.
Results
RXC004 potently inhibited proliferation in vitro in several
genetically selected cell lines. Mechanistically RXC004 arrested
the cell cycle at the G1/S and G2/M cell cycle checkpoints. Axin2
mRNA expression was potently inhibited by RXC004 (sub-nM) across
all RNF43 mutant and RSPO fusion cell lines tested. Furthermore,
inhibition of c-Myc expression correlated with the
anti-proliferative effects of RXC004. In contrast, RXC004 had no
anti-proliferative effects on APC mutant colorectal cancer cells,
and Axin2 and c-MYC expression was not inhibited. In vivo, RXC004
demonstrated significant efficacy and PD responses in multiple
RNF43 mutant and RSPO fusion xenograft models.
Conclusion
Cancer cells carrying RNF43 mutations or RSPO fusions are
sensitive to RXC004 both in vitro and in vivo. This data suggest
RXC004 monotherapy would benefit patients with tumours baring RNF43
mutations or RSPO fusions and support a genetically-defined patient
selection strategy for ongoing RXC004 clinical studies.
The poster, entitled 'Efficacy of the Porcupine inhibitor RXC004
in genetically-defined tumour types' presented at the National
Cancer Research Institute (NCRI) 2018 Cancer Conference in Glasgow,
UK, can be accessed here from noon GMT on 5 November 2018:
https://www.redxpharma.com/app/uploads/2018/11/RXC004-NCRI-2018.pdfE
To learn more about our RXC004 inhibitor programme you can
visit:
https://www.redxpharma.com/programmes/rxc004-porcupine-cancer/
For further information, please contact:
Redx Pharma Plc T: +44 1625 469
920
Lisa Anson, Chief Executive Officer
Andrew Saunders, Chief Medical Officer
Richard Armer, Chief Scientific Officer
Cantor Fitzgerald Europe (Nominated Advisor & T: +44 20 7894
Broker) 7000
Phil Davies
WG Partners LLP (Joint Broker) T: +44 20 3705
9330
Claes Spång/ Chris Lee/ David Wilson
FTI Consulting T: +44 20 3727
1000
Simon Conway/Stephanie Cuthbert
About Redx Pharma Plc
Redx is a UK biotechnology company whose shares are traded on
AIM (AIM:REDX). Redx's vision is to become a leading biotech
focused on the development of novel precision medicines that have
the potential to transform treatment in oncology and fibrotic
diseases.
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END
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