GLS1

SHANGHAI, April 27, 2025 /PRNewswire/ -- Abbisko Therapeutics Co., Ltd. (Abbisko Therapeutics 02256.HK) today announced that it has presented four late-breaking pre-clinical research posters at the 2025 AACR conference held in Chicago, Illinois (USA) from April 25 to April 30. Results were shared for ABSK112 (EGFR exon20ins inhibitor), ABSK131 (PRMT5*MTA inhibitor), and ABK-KRAS-1 (pan-KRAS inhibitor), as well as results from a study investigating potential resistance mechanisms to KRAS G12C inhibitors. Abbisko presented the following posters at the 2025 AACR: Title1: Preclinical Evaluation of ABSK112, a Selective and CNS-penetrant Compound with Strong HER2 Inhibitory Activity for Treating HER2-Driven Solid Tumors Session Category: Late-Breaking Research: Experimental and Molecular Therapeutics 2 Session Date and Time: April 28, 2025, 2:00 PM - 5:00 PM (CDT) Location: Poster Section 54 Poster Board Number: 14 Poster Number: LB240 Conclusion: Our findings establish ABSK112 as a potent, selective and CNS-penetrant HER2 inhibitor, warranting further clinical evaluation of it as a monotherapy or in combination with HER2-targeted ADCs for the treatment of HER2+ cancers with brain metastases. Title 2: Loss-of-Function (LoF) of KEAP1 promotes cell survival through multiple mechanisms, leading to resistance to KRAS G12C inhibitors Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 3 Session Date and Time: April 29, 2025 9: 00AM – 12: 00 PM (CDT) Location: Poster Section 52 Poster Board Number: 1 Poster Number: LB278 Conclusion: KEAP1 LoF mutant NSCLCs develop resistance to KRAS G12C inhibitors through reduced drug-induced ROS accumulation, metabolic adaptation, and sustained activation of MAPK and AKT signaling. Combination therapies targeting glutamine metabolism (e.g., GLS1 inhibitors), MAPK (e.g., MEK inhibitors), and PI3K-AKT-mTOR pathways (e.g., BEZ235) reverse resistance and improve therapeutic efficacy in KEAP1-mutant cell lines. These strategies may restore sensitivity to KRAS G12C inhibitors and enhance clinical outcomes. Title 3: The MTA-Cooperative PRMT5 Inhibitor ABSK131 Exhibits Potent Activity and Broad Synergistic Potential in MTAP-Deleted Cancer Models Session Category: Late-Breaking Research: Experimental and Molecular Therapeutics 4 Session Date and Time: April 30, 2025 9:00 AM - 12:00 PM (CDT) Location: Poster Section 51 Poster Board Number: 9 Poster Number: LB427 Conclusion: ABSK131 exhibits strong anti-tumor activity in MTAP-deleted lung and pancreatic cancer models and synergizes effectively with multiple therapeutic agents. These findings support the continued clinical development of ABSK131 as both a monotherapy and in combination regimens for MTAP-deleted cancers. Title 4: Discovery and characterization of a highly potent and orally available small-molecule inhibitor for diverse KRAS mutations Session Category: Late-Breaking Research: Experimental and Molecular Therapeutics 4 Session Date and Time: April 30, 2025 9:00 AM - 12:00 PM (CDT) Location: Poster Section 51 Poster Board Number: 13 Poster Number: LB431 Conclusion: Taken together, ABK-KRAS-1 exhibits broad in vitro activity against different KRAS mutations and induces dose-dependent tumor regression in KRAS mutated xenograft models. Moreover, ABK-KRAS-1 possesses favorable drug-like properties. Here, ABK-KRAS-1 is presented as a promising therapeutic candidate for the treatment of cancers harboring KRAS mutations. About Abbisko Therapeutics Founded in April 2016, Abbisko Therapeutics Co., Ltd. (HKEX: 02256.HK), is an oncology-focused biopharmaceutical company based in Shanghai that is dedicated to the discovery and development of innovative medicines to treat unmet medical needs in China and globally. The Company was established by a group of seasoned drug hunters with rich research & development and managerial expertise from top multinational pharmaceutical companies. Since its founding, Abbisko Therapeutics has built an extensive pipeline of innovative programs focused on precision oncology and immuno-oncology. Please visit for more information. SOURCE Abbisko WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

[09-October-2023] NEW YORK, Oct. 9, 2023 /PRNewswire/ -- A new combination of treatments safely decreased growth of pancreatic cancer in mice by preventing cancer cells from scavenging for fuel, a new study finds. Led by researchers at NYU Grossman School of Medicine, its Department of Radiation Oncology, and the Perlmutter Cancer Center, the work builds on prior discoveries at NYU Langone that revealed how pancreatic cancer cells, to avert starvation and keep growing, find alternate fuel sources. Normally supplied by the bloodstream, oxygen, blood sugar, and other resources become scarce as the increasing density of fast-growing pancreatic tumors cuts off their own blood supply. In this environment, the ability to switch fuels contributes to the deadliness of pancreatic cancers. Published online October 9 in Nature Cancer, the new study involves a drug designed to prevent pancreatic ductal adenocarcinoma (PDAC) cells from one such switch. PDAC cells use the enzyme glutaminase to convert the amino acid glutamate into glutamine, a form that can be burned for fuel to sustain rapid tumor growth. Drugs designed to block glutaminase, however, have been shown to cause cancer cells to switch to still other scavenging pathways. For this reason, the field next looked at experimental treatments like DRP-104, designed by Dracen Pharmaceuticals, a new "prodrug" form of the compound 6-Diazo-5-oxo-L-norleucine (DON) that is preferentially activated within tumors to overcome toxicity issues seen with DON. DON was designed to starve cancer cells by mimicking glutamine, which unlike glutaminase blockers, broadly inhibits all metabolic pathways that use glutamine. Currently in clinical trials against non-small cell lung cancer, DRP-104 cannot be burned as fuel, but clings to the same enzymes as glutamine. In the current study, DRP-104 treatment alone decreased PDAC growth in mouse models of pancreatic cancer. Importantly, the current team also found that PDAC cells pushed into metabolic crisis by DRP-104 increase signaling through a protein called extracellular signal-regulated kinase or ERK, to make up for their loss of glutamine metabolism. When the team combined DRP-104 with an existing drug that blocks the ERK signaling pathway, trametinib, it further improved survival in pancreatic cancer mouse models compared to DRP-104 treatment alone. "Despite a decade of advances in understanding how cancer cells switch fuel sources, we have not yet effectively translated this into clinically relevant therapies," says corresponding study author Alec Kimmelman, MD, PhD, the Anita Steckler and Joseph Steckler Chair of Radiation Oncology at NYU Langone Health. "Broad antagonism of metabolic pathways with glutamine analogs may provide another mode of attack against these highly resistant tumor cells. The fact that such drugs are already being tested in the clinic makes us hopeful that we may finally see patient outcomes improve, if this approach proves to be effective in clinical trials." Moving forward, the research team will seek to understand how glutamine antagonism impacts other adaptive nutrient scavenging mechanisms in pancreatic cancers and whether these could be targeted as well. The success of such approaches will depend on careful balancing of improved therapeutic efficacy and toxicity from the potential effects on normal tissues, Kimmelman adds. Along with Kimmelman, authors from Perlmutter Cancer Center and the Department of Radiation Oncology at NYU Langone were Joel Encarnación-Rosado, Albert Sohn, Douglas Biancur, Elaine Lin, Victoria Osorio-Vasquez, and Diana González-Baerga. Also Perlmutter authors were Ende Zhao and Diane Simeone. Also authors of the study were Tori Rodrick and Drew Jones from the Division of Advanced Research Technologies at NYU Grossman School of Medicine; Seth Parker from the Department of Biochemistry & Molecular Biology at University of British Columbia in Vancouver, and Yumi Yokoyama and Robert Wild from Dracen Pharmaceuticals, Inc., of San Diego. Funding for the study came from Perlmutter Cancer Center support grant P30CA016087 and National Cancer Institute grants P01A1080192, P01CA117969, R35CA232124, P30CA016087-38, 1R01CA251726-01A1; as well as from the Lustgarten Foundation, Stand Up to Cancer, and the Howard Hughes Medical Gilliam Fellowships. Kimmelman has financial interests in Vescor Therapeutics, is on the scientific advisory board of Rafael/Cornerstone Pharmaceuticals and OncoRev, and has been a consultant for Deciphera and Abbvie. These relationships are being managed according with the policies of NYU Langone Health. Yokoyama and Wild are employees of, and have ownership in, Dracen Pharmaceuticals, maker of DRP-104. Contact: Gregory Williams gregory.williams@nyulangone.org

Predictive Oncology and Cancer Research Horizons partner to drive cancer drugs development. Credit: CDC / Unsplash. Predictive Oncology and Cancer Research Horizons, a part of Cancer Research UK (CRUK), has collaborated to drive cancer drug development using the former’s PEDAL platform. The partnership will use the artificial intelligence (AI) and machine learning platform, PEDAL technology, to determine which cancer types and patient populations are most likely to respond to treatment with Cancer Research Horizon’s pre-clinical drug inhibitors of glutaminase. Predictive Oncology stated that its PEDAL platform makes high-confidence drug response predictions. This helps in more informed drug-tumour type combinations selection for clinical development. By addressing tumour heterogeneity during pre-clinical stages, the platform increases the probability of clinical success. Predictive Oncology CEO Raymond Vennare said: “Our collaboration with Cancer Research Horizons represents a fundamental shift in drug discovery that could lead to the accelerated development of cancer therapies using compounds originating from the CRUK network and developed by Cancer Research Horizons in partnership with their global network. “We now have the ability to impact the most critical stage of early drug discovery in a way that has never been done before.” The company stated that the deal joins non-profit and industry and provides the potential for Cancer Research Horizons to integrate PEDAL technology into the future processes for drug discovery. Cancer Research Horizons and CRUK chief business officer Tony Hickson said: “We are committed to working closely with scientists to discover and advance therapies that can help in the fight against cancer. “Ensuring that patients receive the right treatment for them is of paramount importance and is why we are excited to work with Predictive Oncology to identify the most suitable population for the further development of our compounds.”