Dose escalation, monotherapy trial launched to access the safety and preliminary anti-tumor activity of Debio 0123 in the treatment of advanced solid tumors

LAUSANNE, Switzerland, Dec. 16, 2021 /PRNewswire/ -- Debiopharm (www.debiopharm.com^[1]), 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^[2]). 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^[3] 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^[4] or e-mail alan.lamont@almacgroup.com^[5].

Debiopharm's commitment to patients

Debiopharm develops innovative therapies that target high unmet medical needs in oncology and infectious diseases. Bridging the gap between disruptive discovery products and international patient reach, we identify high-potential compounds and technologies for in-licensing, clinically demonstrate their safety and efficacy and then select large pharmaceutical commercialization partners to maximize patient access globally.

Visit us www.debiopharm.com/^[6]

Follow us @DebiopharmNews at http://twitter.com/DebiopharmNews^[7]

Debiopharm ContactDawn Bonine – Head of Communicationsdawn.bonine@debiopharm.com^[8]Tel: +41 (0)21 321 01 11

References

1. ^{^} www.debiopharm.com (www.debiopharm.com)
2. ^{^} NCT05109975 (clinicaltrials.gov)
3. ^{^} Debio 0123 (www.debiopharm.com)
4. ^{^} www.almacgroup.com/discovery (www.almacgroup.com)
5. ^{^} alan.lamont@almacgroup.com (www.prnasia.com)
6. ^{^} www.debiopharm.com/ (www.debiopharm.com)
7. ^{^} http://twitter.com/DebiopharmNews (twitter.com)
8. ^{^} dawn.bonine@debiopharm.com (www.prnasia.com)