- Featuring next-generation PI3Kα inhibitor and WRN Inhibitor

April 24^th, 2025 — Laekna (2105.HK) announced that the company will present two posters at the 2025 Annual Meeting of the American Association for Cancer Research (AACR), showcasing its internally discovered pre-clinical drug candidates for cancer: LAE118, a pan mutant-selective PI3Kα inhibitor, and LAE122, a novel, potent and selective WRN inhibitor.

Both drug candidates target prevalent tumor mutations. LAE118 targets against PI3Kα mutations, which are commonly found in patients with breast, colorectal, endometrial, and numerous other cancers. LAE122 is a novel, potent WRN-selective inhibitor for the treatment of MSI-H tumors, including colorectal, gastric, endometrial, and ovarian cancers.

Dr. Justin Gu, Chief Scientific Officer of Laekna, said: “Both LAE118 and LAE122 demonstrate robust in vivo anti-tumor efficacy at doses lower than those of competing compounds. Additionally, LAE118 exhibits exceptional in vitro anti-proliferation activities against both kinase and helical domain mutant cells, with IC50 5 to 10-fold lower than those of competing compounds. This positions LAE118 as a promising candidate, offering patients a more precise and effective innovative therapy”.

Dr. Justin Gu emphasized that Laekna’s AI-powered structure-based drug design platform enabled the rapid identification of high-potency candidates with optimized drug-like properties by internal discovery team.  

The AACR Annual Meeting, the most important cancer meeting in the world, will take place from April 25 to 30, 2025, in Chicago, USA.

LAE118: A next-generation PI3Kα inhibitor, potentially best-in-class  

Three hotspot mutations (H1047R, E545K, E542K) on the p110α subunit of PI3Kα are the recognized activating mutations accounting for more than 1/3 of all PI3Kα mutations. Some pan-mutant selective PI3Kαinhibitors demonstrated improved therapeutic window comparing with orthosteric PI3Kα inhibitors and maintained good clinical responses. However, due to relatively weak potency against PIK3CA helical domain mutants, these inhibitors have less favorable clinical responses in these group of patients. Therefore, there is an urgent need to develop novel pan-mutant selective PI3Ka inhibitors with improved activity against helical domain mutants, which would significantly expand the treatable patient population.

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. Currently, no pan-mutant-selective PI3Kα inhibitor has been commercialized. With its potentially best-in-class features, LAE118 has emerged as a key player for the next generation of PI3Kα inhibitors. It’s currently in IND enabling stage.

LAE122: a novel, potent and selective WRN Inhibitor for the treatment of MSI-H tumors

DNA mismatch repair (dMMR) deficiency causes Microsatellite instability (MSI-H), which is frequently observed in various tumor types, including colorectal, gastric, endometrial, and ovarian cancers. Although immune checkpoint inhibitors (ICI) have been approved for the treatment of MSI-H tumors, significant unmet medical need remains across several tumor types that fail to respond or relapse with ICI therapies. Werner syndrome ATP-dependent helicase (WRN) is a RecQ family helicase that plays important roles in DNA repair and in the maintenance of genome integrity. Recent studies have identified WRN as a promising synthetic lethal drug target for MSI-H cancers.

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. In SW48 and HCT116 CDX models, LAE122 showed robust anti-tumor growth effect at lower doses than bench-mark molecules with strong evidence on biomarker change. LAE122 didn’t have off-target liability in in vitro assays and demonstrated good tolerability in preclinical toxicology studies.

Presentation details are as follows:

Poster No.1

Abstract Number: 9661

Poster Number: LB437

Title: LAE118, a Pan Mutant-Selective PI3Kα inhibitor with Strong Anti-tumor Growth Effects in both PIK3CA Kinase and Helical Domain Mutant Xenografts

Time: Wednesday, April. 30, 2025, 09:00 a.m. – 12:00 p.m.  CST

Location: McCormick Place Convention Center, Chicago, Illinois

Poster No.2

Abstract Number: 6302

Poster Number: 4192

Title: Preclinical Characterization of LAE122, a Novel, Potent and Selective WRN Inhibitor for the Treatment of MSI-H Tumors

Time: Tuesday, April. 29, 2025, 09:00 a.m. – 12:00 p.m.  CST

Location: McCormick Place Convention Center, Chicago, Illinois

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About Laekna

Stock Code: 2105.HK

Founded in 2016, Laekna is a science-driven, clinical-stage biotechnology company committed to bringing novel therapeutics to patients with metabolic diseases, cancer and liver fibrosis around the world.

As of December 31, 2024, Laekna has initiated seven clinical trials for LAE102, LAE002 (afuresertib), LAE001 and LAE005 to address unmet medical needs in obesity and cancers.

LAE102 is our internally discovered antibody against ActRIIA. Blocking Activin-ActRII pathway could promote muscle regeneration and decrease fat mass, this positions LAE102 as a promising drug candidate for achieving quality weight control. We’ve obtained IND approvals from the FDA and the CDE for LAE102 in obesity indication and are advancing the Phase I clinical trial in China. In November 2024, Laekna entered into a clinical collaboration agreement with Eli Lilly and Company to support and accelerate global clinical development of LAE102 for the treatment of obesity.

Laekna team has accumulated tremendous experiences and deep know-how in the specific field of targeting ActRII receptors and is developing more drug candidates (LAE103 and LAE123), in addition to LAE102, to maximize the value of the target. LAE103 is an ActRIIB-selective antibody and LAE123 is a dual inhibitor against ActRIIA/IIB. Both are our internally discovered antibodies for muscle and other disease indications.

In the cancer area, Laekna has built a comprehensive portfolio of drug candidates including LAE002(afuresertib), LAE001 and other seven pre-clinical drug candidates. LAE002 (afuresertib) is a potent AKT inhibitor that inhibits all three AKT isoforms (AKT1, AKT2 and AKT3) as well as one of the only two AKT inhibitors in late-stage development for breast and prostate cancer globally. Laekna has commenced the Phase III clinical trial (AFFIRM-205) for LAE002 in patients with HR+/HER2- breast cancer and the study recruitment is on track.

Laekna, Inc. (2105.HK) was listed on the Main Board of The Stock Exchange of Hong Kong Limited (the “Hong Kong Stock Exchange”) on June 29, 2023.

For more information, please visit: https://www.laekna.com/  or https://www.linkedin.com/company/74110713/

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