On April 7, 2024 Laekna (2105.HK) reported that the company has presented two internally-discovered preclinical candidates, in addition to a poster presentation on a clinical trial, at the 2024 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in San Diego, California (Press release, Laekna Therapeutics, APR 7, 2024, View Source [SID1234641848]). The presentations featured preclinical data of two novel selective inhibitors, LAE119, a novel PARP1 selective inhibitor and trapper, and LAE120, a novel selective USP1 inhibitor.
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"After advancing LAE102, our internally discovered antibody against ActRIIA, into IND stage, Laekna continues to strengthen our internal discovery efforts, with new drug candidates emerging", said Dr. Justin Gu, Chief Scientific Officer of Laekna. "The MOA of LAE119 and LAE120 is synthetic lethality, both exhibit strong anti-tumor efficacy and good safety in preclinical models. LAE 119 is a PARP1-selective inhibitor with the strongest DNA-trapping activity among all the PARP inhibitors tested. It shows good activity even in tumor cells with low PARP1 protein level. LAE120 is a novel USP1 inhibitor currently at IND-enabling studies stage. It has a unique chemical scaffold differentiated from all the other disclosed USP1 inhibitors and is expected to induce a different conformational change in USP1. The quick advance of these two projects into PCC stage demonstrates the effectiveness of the close collaboration among Med Chem, Biology and AIDD (AI-driven Drug Discovery) teams. Laekna will continue our internal effort of discovery novel drug candidates to provide more options for patients."
Laekna’s internal discovery focuses on innovation, scarcity, and differentiation, covering three areas: cancer, metabolic diseases，and liver fibrosis. The company has internally discovered 14 drug candidates, among which seven have been optimized and advanced to PCC (pre-clinical candidate) stage. The company plans to have one drug candidate entering the clinical stage each year.
The Annual Meeting of AACR (Free AACR Whitepaper) is set for April 05 to 10, 2024 at the San Diego Convention Center, California, USA. It is the focal point of the cancer research community, where scientists, clinicians, other health care professionals, survivors, patients, and advocates gather to share the latest advances in cancer science and medicine. [1]
[1] View Source
Presentation details are as follows:
Title: Preclinical characterization of LAE119, a novel PARP1 selective inhibitor and trapper
Authors: Ming Li, Yan Chen, Junyan Chen, Ling Jiang, Xiaofen Lin, Justin Gu
Session Category: Experimental and Molecular Therapeutics
Session Title: DNA Damage and Repair
Session Date and Time: Wednesday, Apr 10, 2024 9:00 AM- 12:30 PM (PT)
Location: Poster Section 22
Poster Board Number: 27
Abstract Highlights:
LAE119 is a potent and selective PARP1 inhibitor and PARP1-DNA trapper. It demonstrates more than 1000-fold selectivity for PARP1 DNA trapping activity over PARP2. In comparison to most PARP inhibitors including AZD5305, LAE119 exhibits extremely long residence time on PARP1 in both biochemical and cellular assays and shows good activity even in tumor cells with low PARP1 protein level. It demonstrates robust anti-tumor effect in BRCA2-/- DLD-1 and MDA-MB-436 Xenograft models and has minimal effects on hematologic parameters.
Full texts of the abstracts are available here.
Title: Preclinical candidate LAE120, a novel selective USP1 inhibitor shows effective anticancer and combination activity with PARP inhibitors
Authors: Jintao Wang, Yan Chen, Junyan Chen, Ling Jiang, Xiaofen Lin, Chaojun Cai, Minhua Zhang, Ming Li, Justin Gu
Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Antitumor Agents 2
Session Date and Time: Sunday, Apr 7, 2024 1:30 PM- 5:00 PM (PT)
Location: Poster Section 27
Poster Board Number: 16
Abstract Highlights:
LAE120 is a novel, allosteric and highly potent USP1 inhibitor, displaying monotherapy potency and combination activity with PARP inhibitor in HRD (homologous recombination deficiency) cancers. It has a unique chemical structure differentiated from all the other disclosed USP1 inhibitors and is expected to induce a different conformational change in USP1. LAE120 shows robust tumor inhibitory activity in MDA-MB-436 and K562 xenograft models as a single agent and exhibits synergistic effect in combination with PARP inhibitors. LAE120 demonstrates good therapeutic window in DRF study and is currently at IND-enabling stage.