First potential tyrosine-kinase inhibitor for AML treatment
(single agent or in combination)
● Mechanism of Action:
Multi-target kinase inhibitor
● Proposed indications:
Single or Combination Agent Acute Myeloid Leukemia (AML)
Other indications:
● Patent protection:
● Route of administration:
Development Phase:
Competition:
Chronic Myeloid Leukemia (CML), Acute Lymphoid
Leukemia (ALL), Chronic Lymphoid Leukemia (ALL), Myelodysplastic
Syndrome (MDS)
2026
IV route
Phase I clinical dose-escalation evaluation
Elacytarabine, Sorafenib, Panobinostat
1. RATIONALE AND BACKGROUND
SAR103168 is a novel multi-targeted kinase inhibitor active in various AML models including immature CD34+
AML cells expressing functional P-glycoprotein (P-gp). SAR103168 was developed to target immature AML cells
that are generally believed to be a reservoir of chemo-resistant AML progenitor malignant cells. It is thought
that this reservoir of malignant cells refuels the AML cell clones and triggers the relapse after front-line therapy.
The effect of SAR103168 on both tumor cells and bone marrow angiogenesis in preclinical studies warrants
clinical investigation of the anti-leukemia efficacy of the drug in this difficult-to-treat patient population.
2. MARKET
The leukemia market is segmented due to a broad variety of histopathological disorders. Among acute
leukemias, AML is the most common myeloid leukemia in adults representing 90% of all adult acute leukemias
newly identified each year and 11 920 new patients diagnosed in the US (elderly and children).
3. COMPOUND PROFILE

SAR103168 is a potent inhibitor of the Src kinase family (SKF), the Bcr-Abl kinase and several
angiogenic receptor kinases such as vascular endothelial growth factor receptor type 1 and type 2
(VEGFR1 and VEGFR2), Tie2, platelet-derived growth factor receptor (PDGFR), fibroblast growth factor
receptor (FGFR), and epidermal growth factor receptor (EGFR).

Highly active in vitro and in vivo human AML models as single agent:
o In vitro, SAR103168 has nanomolar potency, specifically against the proliferation of immature
CD34+ AML leukemia cells expressing functional P-gp. Compared to cytarabine, dasatinib or
tipifarnib, SAR103168 has a larger spectrum of activities on immature AML cells.
o In vivo, SAR103168 demonstrates very potent antitumor efficacy in several AML or CML
models when assessed via multiple administration routes. Preclinical efficacy is improved in
AML models compared to Tipifamib and Dasatinib previously developed in the same
indication.

Highly active in in vivo human AML models in combination with cytarabine and daunorubicin.

Phase I Study Experience
o SAR103168 is supplied for IV administration. A Phase I Dose-escalation, Safety and
Pharmacokinetic Study of SAR103168 in Patients Refractory/Relapsed Acute Leukemias or
High-risk Myelodysplastic Syndromes; SAR103168 is administrated as a single agent by
intravenous infusion, once daily for 5 days.
o Based on pharmacokinetic considerations, the dose-escalation portion of the study was
discontinued prior to reaching MTD and further development of the compound was halted
internally.
4. PRELIMINARY SAFETY AND PHARMACOKINETIC PROFILE
Pharmacokinetic and toxicokinetic studies following IV infusion of SAR103168 indicate that the drug behaves
similarly in the rodent (rat) and non-rodent (dog) species used in the toxicology assessment. The compound is
highly protein bound (>99%), widely distributed and eliminated extensively by the biliary route (>80%
recovered in feces).
5. VALUE PROPOSITION

High unmet medical need, high disease burden in terms of mortality and cost despite existing
st
nd
therapeutic options. There are no durable therapeutic options in the 1 line or 2 line AML setting.
 Aimed at the difficult-to-treat older AML population (>60 years); in particular the patients that are not
eligible for treatment with induction chemotherapy.
6. CONTACTS
Guy CLAUDE
Anne Marie SIGOT
Vice President Out-Licensing &Special Projects
Senior Manager Out-licensing and Special Projects
Strategy & Business Development
Strategy & Business Development
Corporate Licenses
Corporate Licenses
[email protected]
[email protected]