PARPBP

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

Drugs that interfere with a way tumors repair damage to their DNA have become valuable tools for treating certain cancers. Some big pharmaceutical companies are developing drugs that improve on this approach, and Merck KGaA is getting its contender by striking a deal with Jiangsu Hengrui Pharmaceuticals. Per deal terms announced Monday, Merck KGaA will pay Hengrui €160 million (about $169 million) up front for global rights, except China, to HRS-1167, a small molecule belonging to a class of drugs called PARP inhibitors. Milestone payments could bring China-based Hengrui up to €1.4 billion ($1.48 billion). PARP enzymes are key to DNA damage response, a mechanism for fixing the damage resulting from the rapid proliferation of cells characteristic of cancer progression. By targeting and blocking these enzymes, PARP inhibitors prevent those repairs, which in turn leads to cell death. Lynparza from AstraZeneca and GSK’s Zejula blazed the trail for PARP inhibitors. Those commercialized drugs broadly address PARP enzymes to treat ovarian cancer, fallopian tube cancer, and primary peritoneal cancer. Hengrui’s drug is a “next-generation” PARP inhibitor designed to be a more potent and selective blocker of the PARP1 enzyme. In Monday’s announcement, Merck KGaA said specifically targeting the PARP1 enzyme offers the opportunity to expand PARP inhibition in both established and new indications. The company points to Phase 1 data showing encouraging signs of clinical activity and patient benefit as a monotherapy. Merck KGaA also noted that compared with first-generation PARP inhibitors, HRS-1167 offers greater potential for use in combination with chemotherapy as well as novel cancer drugs. Hengrui’s drug is joining a Merck KGaA pipeline that includes programs addressing other targets in the DNA damage response cascade, such as ATR, ATM, and DNA-PK. Gilead Sciences entered the chase for a selective PARP1 inhibitor earlier this year with the acquisition of privately held Xinthera and its preclinical PARP1-targeting small molecules. AstraZeneca is further ahead with AZD5305, a PARP1-blocking drug currently in Phase 2 testing as part of combinations that include Enhertu and datopotamab deruxtecan, two antibody drug conjugates (ADC) from its partnership with Daiichi Sankyo. Merck KGaA’s Hengrui deal could also yield an ADC. The agreement grants the German company the option to license global rights, excluding China, to SHR-A1904. This Hengrui ADC addresses Claudin-18.2, a protein abundant in gastric, pancreatic, and esophageal cancers. Merck KGaA said the Hengrui asset is complementary to its own ADC portfolio, which uses different technologies to link the drug payload to the targeting antibody. Merck KGaA’s ADC M9140 is in early-stage clinical development in metastatic colorectal cancer. “This partnership with Hengrui fully aligns with both our external innovation ambition and our oncology research and development strategy by diversifying our robust internal pipeline in our focus areas of DNA damage response inhibition and antibody-drug conjugates,” Danny Bar-Zohar, global head of research & development and chief medical officer for Merck KGaA’s healthcare business, said in a prepared statement. “The synergies of these assets with our portfolio offer broad potential for development and the opportunity to advance more therapeutic options for patients with difficult-to-treat cancers.”

LIANYUNGANG, China, Oct. 30, 2023 /PRNewswire/ -- Jiangsu Hengrui Pharmaceuticals Co., Ltd ("Hengrui Pharma"), a global pharmaceutical company focused on scientific and technological innovation, today announced a licensing agreement with Merck KGaA, Darmstadt, Germany, a leading science and technology company, for its next-generation potent and selective PARP1 (poly (ADP-ribose) polymerase 1) inhibitor, HRS-1167. This is Hengrui's first strategic collaboration with a global pharmaceutical company. The agreement includes an option to an exclusive license for its innovative Claudin-18.2 antibody drug conjugate (ADC) SHR-A1904. "Given the high unmet need in oncology, we are excited to work closely with Merck KGaA, Darmstadt, Germany, to bring Hengrui's innovations to cancer patients worldwide," said Frank Jiang, board member and Chief Strategy Officer of Hengrui Pharma. "Partnering with Merck KGaA, Darmstadt, Germany, on our PARP franchise is an important milestone on Hengrui's globalization journey. We look forward to advancing our molecules rapidly through development and reaching patients in need." Under the terms of the agreement, Merck KGaA, Darmstadt, Germany, will provide Hengrui Pharma with an upfront payment of €160 million. Hengrui Pharma will receive payments for technology transfer as well as an option exercise for the Claudin-18.2 ADC for up to €90 million. Upon the achievement of certain development, regulatory and commercial milestones, Hengrui is eligible to receive royalty payments on net sales of such products by Merck KGaA, Darmstadt, Germany. Potential payments may total up to €1.4 billion with up to double-digit royalty payments. "This partnership with Hengrui fully aligns with both our external innovation ambition and our oncology research and development strategy by diversifying our robust internal pipeline in our focus areas of DNA damage response inhibition and antibody-drug conjugates," said Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business of Merck KGaA, Darmstadt, Germany. "The synergies of these assets with our portfolio offer broad potential for development and the opportunity to advance more therapeutic options for patients with difficult-to-treat cancers. We look forward to leveraging the significant expertise of Hengrui and our strong collaboration ahead." Merck KGaA, Darmstadt, Germany, will receive exclusive rights to develop, manufacture and commercialize HRS-1167 worldwide, outside of mainland China, an exclusive option to develop, manufacture and commercialize SHR-A1904 worldwide, outside of mainland China, and an option to co-promote HRS-1167 and SHR-A1904 in mainland China. About HRS-1167 and SHR-A1904 HRS-1167 is a selective, highly active and orally available PARP1 small molecule inhibitor internally developed by Hengrui with intellectual property rights, which belongs to the second generation of PARP inhibitors. Poly (ADP-ribose) polymerase (PARP) is key in DNA repair pathways. Compared to first-generation PARP inhibitors, HRS-1167 has higher selectivity and affinity for PARP1 and induces DNA trapping. HRS-1167 is currently in early clinical development (Phase 1) and has the potential to be used as a monotherapy and as part of a combination therapy for treating a wider range of patients. SHR-A1904 is an antibody drug conjugate (ADC) targeting Claudin 18.2, internally developed by Hengrui with intellectual property rights. It binds to the target antigen on the surface of tumor cells, allowing the drug to be endocytosed by cells and releasing a small-molecule toxin to kill tumor cells. The product is currently in clinical Phase 1 trials in China, U.S. and Australia. Currently, no Claudin 18.2 targeting ADC product has received marketing authorization. About Hengrui Pharma Hengrui Pharma is an innovative global pharmaceutical company focused on unmet clinical needs, with a strong track record of scientific and technological innovation. Since its first innovative drug approval in 2011, Hengrui Pharma has invested more than 33 billion yuan in R&D and set up 14 R&D centers in Lianyungang, Shanghai, the U.S. and Europe. It has 8 major manufacturing sites and a global R&D team of more than 5,000 professionals. Hengrui Pharma has independently established a number of leading technology platforms such as its ADC platform, proteolysis targeting chimera (PROTAC), molecular gels, bi/multi-specific antibodies, and AI molecular design, which provide a strong foundation for innovative R&D. Hengrui strives for continued innovation and collaboration with global partners to serve a healthy China and benefit patients around the world. Media Contact: Su Zhang su.zhang.sz1@hengrui.com SOURCE Jiangsu Hengrui Pharmaceuticals Co., Ltd