The study was led by Professor Xu Binghe, an academician of the Chinese Academy of Engineering and from the Cancer Hospital of the Chinese Academy of Medical Sciences. The findings indicate that the combination regimen of LAE002 (afuresertib) in combination with fulvestrant was well-tolerated and had promising antitumor activities against pretreated, advanced HR-positive, HER2-negative breast cancer. 

Single-dose administration of LAE102 by IV or SC injection demonstrated a favorable safety profile in the healthy participants. LAE102 exhibited apparent nonlinear clearance saturation at concentrations of approximately 2~4 μg/mL, a threshold that coincided with the sustained PD effect of LAE102, maintaining Activin A levels more than 2-fold above the baseline. The robust PK/PD correlation suggests potential efficacy and supports further clinical development of LAE102 in overweight and obese populations.

The findings indicate that ActRIIA is a major regulator of muscle growth and fat loss in mice. LAE102 shows great potential as muscle preserving weight loss management with a favorable safety profile. On the other hand, LAE123 could be utilized to treat diseases requiring completely inhibition of both ActRIIA and ActRIIB, such as spinal muscle atrophy.

LAE118 is a novel allosteric pan-mutant selective PI3Kα inhibitor demonstrating excellent in vitro anti-proliferation activities in both kinase and helical domain mutant cells. LAE118 presents strong anti-tumor efficacy and good PK/PD relationship in GP2D (H1047L), HCC1954 (H1047R), MCF7 (E545K) and MDA-MB-361 (E545K) Xenograft models at doses that are significantly lower than other pan-mutant selective PI3Kα inhibitors.

LAE122 is a novel, potent and selective WRN inhibitor developed by Laekna through structure-based drug design strategy. LAE122 has highly differentiated structure from bench-mark molecules and displayed single digit nanomolar IC50 values in biochemical assay and cell anti-proliferation assay on MSI-H cells but had no effect on Microsatellite stability (MSS) cells up to 10 µM. LAE122 demonstrated favorable drug-like properties, including good in vitro ADMET and in vivo PK with low plasma clearance and high oral bioavailability across animal species. 

LAE118 is a novel allosteric pan-mutant selective PI3Kα inhibitor. LAE118 demonstrates excellent in vitro anti-proliferation activities in PI3Kα mutant cell lines and remains active against cells resistant to orthosteric PI3Kα inhibitors. LAE118 shows strong anti-tumor growth effect in Xenograft models at a dose that is much lower than other allosteric inhibitors and has less effect on glucose homeostasis compared to orthosteric PI3Kα inhibitors. In pre-clinical toxicology studies, LAE118 also demonstrated good tolerability. These data indicate that LAE118 offers improved efficacy and larger safety window.