Recludix Pharma Presents Data Demonstrating Oral STAT3 Inhibitors Drive Differentiated Efficacy and Safety in Preclinical Models of Th17 Mediated Skin Inflammation in Oral Plenary Session at SID Annual Meeting
May 17 2024 - 3:00PM
Recludix Pharma, a leader in discovery of inhibitors of challenging
targets for inflammatory disease and cancer, presented new data
today in an oral plenary presentation at the Society for
Investigative Dermatology (SID) Annual Meeting titled “Oral
selective STAT3 inhibitors demonstrate differentiated efficacy and
safety potential in preclinical models of Th17 mediated skin
inflammation” (abstract #738). Recludix’s senior vice president of
biology, Paul Smith, Ph.D., reviewed preclinical data on the
company’s potent, selective, and orally bioavailable small molecule
STAT3 inhibitors, including REX-7117. Data demonstrated that
REX-7117 achieves deep, durable, and selective STAT3 inhibition and
exhibits similar efficacy to biologics targeting IL-17 in in vivo
models of plaque psoriasis. Data was also presented that, unlike
JAK1/2 and TYK2 inhibitors, REX-7117 does not impair broader immune
responses, such as interferon-dependent anti-viral immunity or
growth factor signaling critical for hematologic homeostasis.
“These exciting data on our oral STAT3 inhibitors demonstrate
that deep STAT3 inhibition has the potential to drive potent
efficacy -- such as that seen with clinically validated biologics
but with improved convenience as an orally-administered medication,
while high selectivity for the downstream STAT3 target may avoid
some of the safety concerns observed with JAK and TYK2 inhibitors,”
said Ajay Nirula, M.D., Ph.D., executive vice president and head of
research and development. “Inhibiting STAT3 could be a favorable
and effective approach to treating Th17- and Th1-mediated diseases,
such as psoriasis, psoriatic arthritis, rheumatoid arthritis, and
inflammatory bowel disease.”
Both REX-7117 and REX-5376 are highly potent and selective
orally-available STAT3 inhibitors, as demonstrated across
biochemical and cellular assays, which have the potential to:
- Impair inflammatory Th17 cell
function, while sparing activation of other cytokine pathways which
play critical roles in the defense against viruses, bacteria, extra
cellular pathogens, and parasites
- Spare STAT1 mediated-signaling, in
contrast to the impact on STAT1 signaling seen with baricitinib
(JAK1/2) and deucravacitinib (TYK2)
- Not impair either type I or type II
interferon (IFN)-mediated antiviral activity, as shown in in vitro
models
- Not impair STAT5-mediated signaling
by hematopoietic growth factors, unlike some JAK inhibitors which
have the risk of inducing anemia, thrombocytopenia, and
neutropenia
In a murine IL-23 induced psoriasis model, REX-7117 achieved
efficacy responses similar to an anti-IL-17A antibody surrogate
treatment and was more efficacious than an estimated clinically
relevant dose of deucravacitinib.
About STAT3The interleukin cytokines IL-23 and
IL-6 signal through STAT3 and promote the generation and function
of pathogenic T helper type-17 (Th17) cells, a type of immune cell
that is pro-inflammatory. Th17 cells are considered pivotal players
in certain inflammatory diseases, including rheumatoid arthritis,
psoriasis, inflammatory bowel disease and others. Inhibiting STAT3
can also offer potential efficacy beyond Th17 / IL-17 driven
diseases in clinical indications where blocking the IL-6 pathway is
clinically validated. Furthermore, clinical trials inhibiting
oncostatin M (OSM) and IL-22, both STAT3 dependent cytokines, have
been reported as efficacious in inflammatory disease.
A selective, oral STAT3 inhibitor has potential to provide an
attractive alternative to JAK/TYK2 inhibitors and biologics for
multiple inflammatory diseases.
STAT3 inhibitors may also have significant opportunity in cancer
settings, as STAT3 is activated in greater than 70% of human
cancers.
About RecludixRecludix is a leader in
developing platform approaches to discover potent and selective
inhibitors of challenging protein targets. The company’s management
team includes industry veterans with a track record of success,
including former leaders of Seagen, Blueprint Medicines, and Lilly.
Recludix has developed a unique drug discovery platform that
integrates custom generated DNA-encoded libraries, massively
parallel determination of structure activity relationships, and a
proprietary screening tool to ensure selectivity. The company is
employing this approach first in the development of SH2 domain
inhibitors. Recludix’s most advanced programs are focused on STAT
(signal transducer and activator of transcription) proteins where
abnormal activation is found in inflammatory diseases, such as
rheumatoid arthritis, asthma, atopic dermatitis, and inflammatory
bowel disease, as well as numerous cancer types, such as multiple
leukemias and lymphomas. The company has a strategic partnership
with Sanofi for the development and commercialization of a STAT6
inhibitor. Recludix is also advancing STAT3 inhibitors for
Th17-mediated I&I diseases and oncology indications, as well as
additional programs. For more information, please visit the
company’s website at https://recludixpharma.com.
Recludix Contacts:Alexandra Santos
asantos@wheelhouselsa.com
Aljanae Reynoldsareynolds@wheelhouselsa.com