Afuresertib

SHANGHAI and WARREN, N.J., April 7, 2024 /PRNewswire/ -- Laekna (2105.HK) announced 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) in San Diego, California. 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. "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 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] 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. Full texts of the abstracts are available here. About Laekna Founded in 2016, Laekna is a science-driven, clinical-stage biotechnology company committed to bringing novel therapies to cancer, metabolic diseases and liver fibrosis patients worldwide. As of December 31, 2023, we have initiated six clinical trials for Afuresertib (LAE002), LAE001 and LAE005 for the treatment of breast cancer, prostate cancer, ovarian cancer and PD-1/ PD-L1 drug-resistant solid tumors to address the unmet medical needs. Among the six clinical trials, three are multi-regional clinical trials (MRCTs). 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 or completed the pivotal-stage clinical development for anti-cancer treatment globally. Laekna's internal drug discovery platform has discovered 14 drug candidates. LAE102 is our internally discovered antibody against ActRIIA. We've submitted IND applications to CDE and FDA respectively for LAE102 in relation to obesity in the first quarter of 2024. Blocking Activin-ActRII pathway could promote skeletal muscle regeneration and decrease fat mass. Laekna team has accumulated tremendous experiences and deep knowhow in this specific field and is developing more drug candidates (LAE103 and LAE123) to maximize the value of targeting ActRII receptors. Laekna, Inc. was listed on the Main Board of The Stock Exchange of Hong Kong Limited (the "Hong Kong Stock Exchange") on June 29, 2023, with the stock code 2105.HK. For more information, please visit: or Forward Looking Statements This press release may contain certain "forward-looking statements" which are not historical facts, but instead are predictions about future events based on Laekna's current beliefs, assumptions, and expectations, commonly identified by words such as "would", "may", "expects", "believes", "plans", "intends", "projects" and other terms with similar meaning. Although we believe that our predictions are reasonable, future events are inherently uncertain and our actual future results or performance may be materially different from what we expect. Accordingly, you are strongly cautioned that reliance on any forward-looking statements is subject to significant known and unknown risks and uncertainties. All forward-looking statements contained herein are qualified by reference to the cautionary statements set forth in this section. All information provided in this press release is as of the date of this press release and are based on assumptions that we believe to be reasonable as of this date, and we do not undertake any obligation to update any forward-looking statement, except as required under applicable law. SOURCE Laekna

Takeda's licensing deal with Protagonist Therapeutics, Lonza's plant closure and the House BIOSECURE bill targeting certain Chinese biotechs made our news this week. Takeda paid $300 million upfront to license a blood disorder candidate. Lonza will close a biologics plant in China. A U.S. draft bill targets several Chinese biotech companies. And more. 1. Takeda acts as Protagonist, paying $300M for licensing rights to late-stage hematology asset Takeda agreed to pay $300 million upfront to in-license Protagonist Therapeutics’ rusfertide, a hepcidin mimetic designed to treat polycythemia vera, a rare chronic blood disorder. Protagonist could eventually choose to co-commercialize the drug in the U.S. or opt for higher milestone and royalty payments. The drug had its FDA breakthrough designation pulled in 2022 because of “observed malignancies.” 2. Lonza closes plant in China but CDMO's sales signal an uptick in industry Lonza has confirmed that it will shutter a biologics production plant in Guangzhou, China. The site was opened in 2021 and employs 400. This closure, along with Lonza’s plan to close another facility in Hayward, California, will begin this quarter and end in the first quarter of 2025. The Swiss CDMO giant also reported a chairman transition and quarterly earnings that exceeded expectations. 3. WuXi Biologics plays defense after US bill brands certain Chinese biopharmas as security threats A House committee unveiled a bill targeting so-called “foreign adversary biotech companies of U.S. national security concern.” The proposed bill would ban certain Chinese biotechs from accessing U.S. government contracts. WuXi AppTec, WuXi Biologics and BGI are listed as “companies of concern.” WuXi Bio’s stock plummeted at the news, and the company put out statements seeking to clarify the situation. 4. Daiichi Sankyo again dials up Enhertu sales forecast, advances 2nd AstraZeneca-partnered ADC Daiichi Sankyo has increased its forecast for AstraZeneca-partnered Enhertu to now expect the antibody-drug conjugate to collect 383.9 billion Japanese yen ($2.6 billion) for the 12 months ending March 31. However, the improvement comes from outside the U.S., as the company reduced the drug’s U.S. sales estimate by $30 million to $1.58 billion. 5. After GSK and Novartis handoffs, Laekna's drug fails ovarian cancer trial Shanghai-based Laekna said its ATK inhibitor afuresertib has failed in a global phase 2 registrational trial in platinum-resistant ovarian cancer. A combination of the drug and the chemotherapy paclitaxel failed to beat paclitaxel alone at preventing disease progression or death. The Chinese biotech picked up the drug in a licensing deal with Novartis in 2018. 6. Samsung taps Lunit to bring AI detection to its chest X-ray scanners Samsung’s Boston Imaging unit has tapped South Korean artificial intelligence developer Lunit to equip its chest X-ray scanners, GM85 and GC85A Vision, with programs that automatically highlight critical conditions. The deal is built around two AI platforms that together can detect 10 of the most common lung abnormalities. Samsung will also help Lunit validate AI solutions for other conditions such as an enlarged heart muscle, calcification, fibrosis and tuberculosis. Other News of Note: 7. FDA slams Eugia with Form 483 and posts older reprimands for AGC, Baxter 8. Singapore's Genetic Design and Manufacturing reels in $21M in series A funding 9. Takeda wins FDA approval for immunoglobulin therapy Gammagard Liquid for CIDP (release)