05.03.2020 – 09:01
Debiopharm advances into the highly anticipated clinical phase for their potent WEE1 inhibitor
Debio 0123 starts first-in-human, dose escalation phase I clinical trial assessing the safety and efficacy of the compound in combination with carboplatin to treat refractory solid tumors
Debiopharm (www.debiopharm.com), a Swiss biopharmaceutical company, announced today the advancement of their first-in-human, phase 1 study with the cancer treatment Debio 0123, an oral, potent and highly selective WEE-1 inhibitor, in combination with carboplatin in patients with advanced solid tumors. This dose escalation trial will be conducted in patients with refractory solid tumors that have recurred or progressed following prior platinum-based chemotherapy and for which no standard treatment is available. Currently one of three WEE1 inhibitors in clinical development, the Debio 0123 program was initiated based on the deepened understanding of the DNA damage response (DDR) of cancer cells.
Initially discovered by the cutting edge biotech company, Almac Discovery, before being licensed by Debiopharm, Debio 0123 has shown anti-tumor activity both as a single agent and in combination with carboplatin in pre-clinical cancer models. The advancement of Debio 0123 into clinical studies may reveal improved therapeutic results for cancer patients.
"This clinical phase of Debio 0123 is highly anticipated in light of the therapeutic potential of the molecule. Pre-clinical research results suggests that this potent WEE-1 inhibitor has the potential to show activity in cancer patients, particularly in combination with DNA damaging treatments, such as chemo- and radiation-therapies" explained Angela Zubel, Chief Development Officer, Debiopharm.
The DNA in cancer cells can be damaged by a variety of treatments such as radiation, antimetabolites, alkylating agents, DNA topoisomerase inhibitors and platinum-based chemotherapy. When this damage occurs, the cells respond by pausing the cell cycle temporarily to allow for DNA repair, hence reducing the effectiveness of cytotoxic therapies against the cancer cells. Treatments such as Debio 0123 which inhibit the DDR are promising drug candidates as they can enhance the effects of DNA damaging therapies and promote a lethal response. The WEE-1 kinase is a key regulator of several cell cycle checkpoints including G2/M. WEE-1 inhibition can force cells in a state of arrest to continue the cell cycle, ultimately leading to cell death. The resulting impairment of the G2-M checkpoint would prevent cancer cells from repairing induced DNA damage, considerably enhancing the effect of the DNA damaging therapy and thus optimizing the therapeutic outcome.
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Debiopharm develops innovative therapies that target high unmet medical needs in oncology and bacterial infections. Bridging the gap between disruptive discovery products and real-world 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.
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Original content of: Debiopharm International SA, transmitted by news aktuell