AB Science SA announced that it has been authorized by the French Medicine Agency, ANSM, to initiate a Phase I/II study (AB18001) evaluating AB8939 in patients with refractory and relapsed AML and refractory myelodysplastic syndrome (MDS). This approval comes just a few weeks after receiving similar authorization from the Canadian Health Authority. As previously communicated, AB8939 is a new generation synthetic microtubule destabilizer with the ability to overcome multidrug resistance and the potential for broad applicability as a potent anticancer drug. Microtubules play a crucial role in multiple cellular functions which makes them an important target for cancer therapy. Indeed, chemotherapies that target microtubules, such as taxanes and vinca alkaloids, are among the most successful anticancer therapeutics available. Unfortunately, the development of drug resistance (for example, via Pgp efflux pumps that transport the drugs out of the cancer cells) often restrict their clinical efficacy. Key characteristics of AB8939 are that it circumvents difficulties associated with Pgp-dependent multidrug resistance and is not deactivated by an enzyme named myeloperoxidase, which is an advantage over existing chemotherapies. Another advantage and distinguishing characteristic of AB8939 is that it is a synthetic drug. The therapeutic potential of AB8939 has been demonstrated through a series of preclinical experiments [2?4]. In vivo data from a highly resistant Ara-C patient derived xenograft (PDX) mouse model showed that AB8939, administered alone or in combination with Ara-C, increased survival relative to single agent Ara-C, with an accompanying significant reduction of blasts in blood and decrease in tumor growth [2]. Ara-C is considered the clinically most relevant cytotoxic drug for AML treatment. In another example, cancerous tumors from patients suffering from resistant acute megakaryoblastic leukemia (an AML subtype) were transplanted into mice. Data showed a complete response in mice treated with AB8939, as compared with rapid disease progression in control animals [3]. No apparent toxicity was observed during the time course of the treatment. The first indication AB8939 is being developed for is acute myeloid leukemia (AML), a rapid proliferating hematological cancer that originates in the bone marrow and quickly moves into the blood. Cytarabine (Ara-C) is the current standard chemotherapy for AML treatment, however, drug resistance is a major limitation to successful therapy. AB8939 therefore has strong potential as a second or third-line treatment in AML patients who are unfit to receive intensive chemotherapy. The advantageous mechanistic characteristics of AB8939 mean that it is potentially applicable to a large number of other oncology indications currently treated by microtubule-inhibitor drugs (such as taxanes and vinca alkaloids) and in particular hematological cancers. The envisioned strategy is to position AB8939 in patients with abnormal cytogenetics that make these patients unresponsive to first-line therapy.