RCS - Redx Pharma plc - Redx Reports Encouraging Zamaporvint Phase 2 Data

AstraZenecaAnnouncement

28/06/2024 08:15

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20240628:nRSb2489Ua&default-theme=true

RNS Number : 2489U  Redx Pharma plc  28 June 2024

 

 

REDX PHARMA LIMITED

("Redx" or the "Company")

Redx Reports Encouraging Zamaporvint (RXC004) Phase 2 Combination Data in MSS
mCRC at ESMO GI Congress Supporting Genetic Selection Hypothesis in
Hard-to-Treat GI Cancers

Zamaporvint in combination with anti-PD-1, in genetically-selected MSS mCRC
patients led to partial responses being observed in ~30% patients, potentially
higher than current SOC and in a setting where anti-PD-1 therapy alone is not
effective

Data supports genetic selection of patients in hard-to-treat GI cancers

Alderley Park, UK, 28 June 2024 Redx Pharma (https://www.redxpharma.com/)
(JPJ:REDX), the clinical-stage, small molecule biotechnology company,
announced data from all Phase 2 clinical trial modules of zamaporvint
(RXC004), a potent, selective, orally-active Porcupine inhibitor in
development for Wnt-ligand dependent, hard-to-treat GI cancers at the European
Society for Medical Oncology Gastrointestinal Cancers (ESMO GI) Congress.

These data were from small, signal searching patient cohorts in the PORCUPINE
study, investigating genetically-selected patients (RNF43_mutant/RSPO-fusion
subgroup) with microsatellite stable metastatic colorectal cancer (MSS mCRC)
as monotherapy and in combination with anti-PD-1 (NCT04907539); and the
PORCUPINE2 study investigating all-comers biliary tract cancer (BTC) as
monotherapy and anti-PD-1 combination, as well as genetically-selected
pancreatic cancer as monotherapy (NCT04907851).

 

Natalie Cook, Chief Investigator for the zamaporvint Study Programme
commented: "It is very encouraging to see the data returned from this
signal-searching study. The indications targeted are in populations with a
particularly poor prognosis and limited treatment options. Wnt inhibition has
long held promise for this genetically-selected patient group and a tolerable,
clinically active Porcupine inhibitor in combination with anti-PD-1 could
potentially offer a new treatment option for patients with these particularly
hard to treat cancers."

 

Dr. Helen Timmis, Interim Chief Medical Officer, Redx Pharma commented: "We
are delighted to report the Phase 2 data from our zamaporvint study programme
which shows a disease control rate of 57% including partial responses in ~30%
of the patients treated with zamaporvint in combination with nivolumab in MSS
mCRC. Real world evidence shows that the prognosis for the RNF43/RSPO mutant
subgroup of MSS mCRC is significantly worse than in MSS mCRC patients without
these Wnt aberrations, where outcomes are already poor. This early signal
indicates that, in the right patient groups, the combination of Porcupine and
immune checkpoint inhibition has the potential to provide a much-needed
improvement on the current standard of care."

 

Zamaporvint has been shown to have a tolerable safety profile and is the first
Porcupine inhibitor to demonstrate efficacy across this hard-to-treat
RNF43/RSPO patient subgroup. Partial responses observed in ~30% (2/7) of
genetically-selected patients when combined with nivolumab in the PORCUPINE
MSS mCRC module is encouraging in a late-line patient population who have
previously undertaken a median of two prior lines of therapy, and where
anti-PD-1 alone is not effective 1  (#_ftn1) . This suggests activity levels
potentially better than late-line standard of care in this setting 2  (#_ftn2)
. Furthermore, a disease control rate ≥16 weeks of 57% (4/7), higher than
zamaporvint monotherapy at 15% (2/13), indicates the potential for zamaporvint
in combination with immune checkpoint inhibition to drive durable efficacy
outcomes. Consistent with this, robust metabolic (FDG-PET) and molecular
(ctDNA) responses were observed in all patients that achieved disease control
(partial response or stable disease) following zamaporvint treatment with or
without nivolumab.

 

The results from the PORCUPINE2 study also showed some durable clinical
benefit in the BTC module in an all-comers (unselected) patient group, albeit
at a lower level than that observed in genetically-selected MSS mCRC. In the
RNF43 mutated pancreatic ductal adenocarcinoma (PDAC) cohort, although one
partial response was observed in the monotherapy module, participant numbers
in the present study are too low to support any conclusion on efficacy.
However, further investigator sponsored studies in this indication are being
planned.

 

In both the PORCUPINE and PORCUPINE2 studies all patients received
prophylactic denosumab that successfully prevented any treatment related bone
effects, a known effect of Wnt inhibition.

 

Overall, the data from these signal searching studies show enhanced activity
of zamaporvint within the RNF43/RSPO MSS subgroup of GI cancers. Furthermore,
they support clinical development in this subgroup in combination with
anti-PD-1 where we see an exciting opportunity for Wnt pathway inhibition by
zamaporvint to reverse innate anti-PD-1 resistance.

 

Other rational zamaporvint combination opportunities to enhance patient
benefit, such as with early line chemotherapies or with EGFR/MAPK pathway
inhibitors, also exist in wider GI cancer patient populations. Redx is seeking
a partner to support ongoing clinical development.

 

A copy of both posters is available on the Company website at:
https://www.redxpharma.com/scientific-publications/
(https://www.redxpharma.com/scientific-publications/)

 

 

About zamaporvint

Zamaporvint (RXC004), is a potent, selective, oral small molecule inhibitor of
the enzyme, Porcupine, a key activator of Wnt-ligands in the Wnt signalling
pathway. Aberrant Wnt signalling contributes directly to tumour growth and
plays an important role in immune resistance to treatment with immuno-oncology
agents such as anti-PD-1 checkpoint inhibitors.

 

Wnt-ligand activation is common in GI cancers and by selecting patients with
tumours that have high Wnt-ligand dependency, such as tumours with mutations
in the RNF43 gene or fusions in the RSPO gene family, zamaporvint has an
opportunity to directly target tumours in addition to potentially reversing or
delaying resistance to multiple conventional and targeted cancer therapies.

 

 

About the PORCUPINE Clinical Study

 

PORCUPINE, (clinicaltrials.gov (http://clinicaltrials.gov/)  NCT04907539) is
focused on genetically-selected patients with aberrated, advanced MSS mCRC
with a histologically confirmed Ring finger protein 43 (RNF43) or R-spondin
(RSPO) mutations who have progressed on more than one prior standard of care
treatment. RNF43/RSPO mutations account for a particularly complex and
difficult to treat patient population with an especially poor prognosis and
limited treatment options. Given the dual mechanism of action of zamaporvint,
which preclinically was shown to inhibit both tumour growth and immune
evasion, there is a strong rationale for immune therapy combination in the MSS
mCRC setting and zamaporvint was evaluated in combination with nivolumab, a
PD-1 inhibitor, as well as a single agent monotherapy.

 

25 patients were enrolled with a median of two prior lines of therapy, with
13/17 being efficacy evaluable from Arm A (zamaporvint monotherapy; 2mg QD)
and 7/8 patients being efficacy evaluable from Arm B (zamaporvint (1.5mg QD)
in combination with nivolumab).

 

 

About the PORCUPINE2 Clinical Study

 

PORCUPINE2, (clinicaltrials.gov (http://clinicaltrials.gov/)
 NCT04907851), evaluated zamaporvint as a monotherapy in patients that had
histologically-confirmed RNF43 mutated pancreatic ductal adenocarcinoma
(PDAC), or evaluated zamaporvint in patients that had molecularly-unselected
biliary tract cancer (BTC; a highly Wnt-ligand expressing cancer) that had
progressed after 1(st) line treatment, as either monotherapy and in
combination with pembrolizumab, a PD-1 inhibitor.

 

45 patients were enrolled, with Module 1 being PDAC patients with a confirmed
RNF43_LoF mutation (M1: N=6), and Modules 2 and 3 being BTC (M2: N=20, M3:
N=19). Patients received zamaporvint monotherapy in M1 and M2 (2mg QD) or in
combination with pembrolizumab for M3 (1.5mg QD). Of the 45 patients enrolled,
37 were efficacy evaluable.

 

 

 For further information, please contact:

 Redx Pharma Limited                                                 T: +44 (0)1625 469 918

 UK Headquarters

 Caitlin Pearson, Head of Communications

 ir@redxpharma.com (mailto:ir@redxpharma.com)

 FTI Consulting                                                      T: +44 (0)203 727 1000
 Simon Conway/ Ciara Martin

 

 

About Redx Pharma Limited

Redx Pharma (JPJ: REDX) is a clinical-stage biotechnology company focused on
the discovery and development of novel, small molecule, targeted therapeutics
for the treatment of fibrotic disease, cancer and the emerging area of
cancer-associated fibrosis. Redx aims to progress its programmes to clinical
proof of concept before evaluating options for further development and
potential value creation. The Company is currently progressing an industry
leading ROCK inhibitor portfolio through the clinic, including zelasudil, a
selective ROCK2 inhibitor for the treatment of interstitial lung diseases
including idiopathic pulmonary fibrosis and RXC008, a GI-targeted pan-ROCK
inhibitor for the treatment of fibrostenotic Crohns disease. Additionally,
the Company has a Phase 2 precision oncology programme, zamaporvint, which it
intends to partner for further development.

The Company has a strong track record of discovering new drug candidates
through its core strengths in medicinal chemistry and translational science,
enabling the Company to discover and develop differentiated therapeutics
against biologically or clinically validated targets. To date, six Redx
discovered molecules have been progressed into the clinic with the Company's
accomplishments evidenced not only by its wholly-owned clinical-stage product
candidates and discovery pipeline, but also by its strategic transactions,
which includes the sale of pirtobrutinib (RXC005, LOXO-305), the only
non-covalent or reversible BTK inhibitor now approved by the US FDA, and
transactions with both AstraZeneca and Jazz Pharmaceuticals.

 

 1  (#_ftnref1) Le et al (2015)

 2  (#_ftnref2) (Fruquintinib ORR 1.5%  FRESCO ; trifluridine/tipiracil +
bevacizumab ORR 6.1%  SUNLIGHT ).

This information is provided by Reach, the non-regulatory press release distribution service of RNS, part of the London Stock Exchange. 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  NRAKDLFLZQLFBBZ