OTS - DEBIOPHARM FURTHER EXPLORES THE POTENTIAL OF ITS POTENT, HIGHLY SELECTIVE WEE1 INHIBITOR DEBIO 0123 IN PHASE 1 CANCER STUDY (part 1)
2021. December 16. 09:00
Lausanne, Switzerland, 16 December, 2021 (APA/OTS) - Dose
escalation, monotherapy trial launched to access the safety and
preliminary anti-tumor activity of Debio 0123 in the treatment of
advanced solid tumors
Debiopharm (www.debiopharm.com), a Swiss biopharmaceutical
company, announced today the first patient treated in the newly
launched open-label, phase I study evaluating Debio 0123, an oral,
potent and highly selective WEE1 inhibitor, as monotherapy in
patients with advanced solid tumors (NCT05109975). Part of an
emerging new class of drugs working within the DNA damage response
(DDR) pathway, the compound's anti-tumor capacity has been
evaluated in several preclinical studies along with the ongoing
phase I study in combination with carboplatin-based chemotherapy.
This new trial's primary objective is to identify the maximum
tolerated dose and/or recommended phase II dose in adults with
advanced solid tumors that have recurred or progressed after prior
therapy and/or for whom no standard therapy of proven benefit is
available.
The development of the Debio 0123 program is rooted in the
growing understanding of the DNA damage response of cancer cells.
Research reveals that cancer cell survival relies on the tightly
regulated cell cycle that pauses at certain points to allow the
repair of damaged DNA so that tumor cells can continue to divide
and grow. WEE1 is a catalyzing enzyme implicated in these "DNA
repair stops" helping cancer to thrive. By inhibiting WEE1, the
cell cycle checkpoints are compromised, driving cancer cells to
start their replicating prematurely, or before the repair of
detrimental DNA damage, ultimately leading to cell death.
Furthermore, WEE1 inhibitors are suspected to selectively target
tumor cells, inducing synthetic lethality without impacting
survival of normal cells. The potential best-in class status of
Debio 0123 relies on its highly selective inhibition against WEE1.
"We're intrigued to learn more about the clinical benefits that
WEE1 inhibition with Debio 0123 alone could offer cancer patients.
We believe that this new modality can effectively exploit the
genomic instability and malfunctioning of the DNA repair process in
cancer cells in hopes that ultimately tumor progression is halted
and patient survival is improved," Dr. Esteban Rodrigo Imedio,
Senior Medical Director, Oncology Research & Development,
Debiopharm. "As Debio 0123 is highly selective against WEE1, in
time, ongoing clinical research could confirm Debio 0123's
potential best-in-class status."
Initially discovered by Almac Discovery before being
in-licensed by Debiopharm in 2017, the evaluation of Debio 0123 as
monotherapy could help to better characterize the safety and
efficacy profile of the compound in a clinical setting and define
the parameters for eventual phase II research. Pre-clinical
research suggests potential activity for cancer patients,
particularly in combination with DNA damaging agents such as chemo-
and radiotherapy. WEE1 inhibitors are promising drug candidates as
they inhibit DDR, offering the possibility to enhance the efficacy
of these agents, frequently part of the standard-of-care of various
cancer types. Debiopharm plans to advance the clinical program
while simultaneously negotiating potential partnerships, such as
during the upcoming JP Morgan 2022 conference, with larger
pharmaceutical companies for eventual commercialization.
Dr. Stephen Barr, Managing Director & President, Almac
Discovery commented, "Since the discovery of our highly selective
WEE1 inhibitor, now known as Debio 0123, we have looked forward
with anticipation to understanding its potential therapeutic
benefit for cancer patients across the globe. We are therefore
delighted that, in addition to the ongoing combination clinical
study, Debio 0123 is also being evaluated as a monotherapy in the
treatment of advanced solid tumors. We look forward to seeing
further progress from this ongoing clinical research."
About Debio 0123
Debio 0123 is a WEE1 kinase inhibitor, a key regulator of the
G2/M and S phase checkpoints, activated in response to DNA damage,
allowing cells to repair their DNA before resuming their cell
cycle. WEE1 inhibition, particularly in combination with DNA
damaging agents, induces an overload of DNA breaks. In conjunction
with abrogation of other checkpoints such as G1, the compound
pushes the cells through cycle without DNA repair, promoting
mitotic catastrophe and inducing apoptosis of cancer cells.
About Almac Discovery
Almac Discovery is an innovative research driven biotech
company dedicated to the discovery and development of First in
Class therapeutics across a range of therapeutic areas including
neuroscience, muscle-wasting, oncology and inflammation. Almac
Discovery focuses on the discovery to preclinical stage, seeking to
licence programmes with a pharmaceutical partner for further
development.
For more information, please visit www.almacgroup.com/discovery
or e-mail alan.lamont@almacgroup.com.
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