The ability to create compounds that affect apoptosis allows new approaches to treat diseases where cell death has an important role, including cancers, hepatitis B and age-related disease.
Ascentage has a four small molecule candidates that act via the several major molecular pathways linked to apoptosis. Each candidate is designed with attributes providing the potential to lead to a best in class or first in class therapy and are being developed to address specific needs in markets around the world.
Candidate Candidate | Molecule Molecule | Condition Condition | Preclinical Pre | Phase I Ph I | Phase II Ph II | Filed Filed | Marketed Mkd |
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BCR-ABL/KIT
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Resistant CML
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GIST
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c-Met Selective
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Cancer (c-Met+)
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FAK/ALK/ROS1
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NSCLC
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Ph + ALL
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SummaryAPG-2449: FAK/ALK/ROS1 Tyrosine Kinase Inhibitor (TKI) for Non-Small Cell Lung Cancer (NSCLC) and other solid tumors APG-2449 is a potent, orally bioavailable inhibitor of FAK, ROS1 and ALK tyrosine kinases. In preclinical models of ALK-positive NSCLC, APG-2449 has demonstrated antitumor activity and the ability to overcome resistant mutations the first generation and second generation ALK inhibitors, including G1202R mutations. In addition, APG-2449 single agent and combination therapy effectively inhibits tumor growth of ALK-positive neuroblastoma in preclinical setting. Through targeting FAK signaling pathway, APG-2449 demonstrates synergistic or enhanced antitumor activity in combination therapy in the preclinical tumor models of mesothelioma, EGFR mutant NSCLC, and ovarian cancer. APG-2449 is currently in clinical development for treatment of patients with NSCLC failed to respond to treatment with earlier-generation ALK inhibitors. Commercial RightsAscentage has global rights. |
Candidate Candidate | Molecule Molecule | Condition Condition | Preclinical Pre | Phase I Ph I | Phase II Ph II | Filed Filed | Marketed Mkd |
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MDM2-p53
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Solid Tumors (IO combo)
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Yao W, Bai L, Wang S, Zhai Y, Sun SY. Mcl-1 levels critically impact the sensitivities of human colorectal cancer cells to APG-1252-M1, a novel Bcl-2/Bcl-XL dual inhibitor that induces Bax-dependent apoptosis. Neoplasia. 2022;29:100798. doi:10.1016/j.neo.2022.100798 |
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Bcl-2/Bcl family
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Duchenne muscular dystrophy
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SummaryLorem ipsum dolor sit amet, consectetur adipiscing elit. Fusce placerat non lectus nec convallis. Cras faucibus, orci sit amet porttitor tristique, velit libero dapibus libero, at pellentesque tellus dolor id elit. Ut eu mi in neque tincidunt condimentum vitae efficitur urna. Aenean convallis lectus a sem tempor, eu rutrum tellus egestas. Vivamus ut tortor at arcu commodo vehicula scelerisque sed ex. Vivamus posuere enim eget sodales ornare. Pellentesque vitae fringilla quam. Quisque turpis neque, varius sed leo sed, convallis consequat risus. Donec pretium fringilla lacinia. Curabitur sollicitudin, erat non finibus elementum, mauris lorem volutpat magna, nec pharetra arcu dolor vitae felis. Nulla tristique ornare mauris, nec imperdiet ipsum vehicula ornare. In et tempor libero. Maecenas vitae magna sit amet ex vehicula posuere. Fusce convallis, libero vel sagittis lobortis, eros nisi mattis nisl, eu suscipit nisi neque vel ligula. Proin lacinia bibendum odio, nec facilisis quam accumsan sed. Sed posuere massa nunc, vitae faucibus nunc gravida nec. Commercial RightsMaecenas euismod, justo at viverra consequat, sapien est condimentum quam, non aliquet orci ex sit amet dolor. Curabitur augue sapien, rhoncus ac arcu et, molestie congue velit. Morbi lorem risus, pharetra ac finibus id, aliquam quis massa. Vivamus id orci id magna venenatis lobortis. Nunc molestie gravida justo non ornare. Suspendisse luctus facilisis ex mollis sollicitudin. Pellentesque at risus lobortis, imperdiet justo in, viverra mi. Suspendisse hendrerit eget lacus vitae rutrum. Duis rhoncus sit amet sem vel gravida. Cras ac nisi eu erat laoreet elementum. Mauris enim tellus, accumsan eu dapibus ac, tincidunt sed enim. Nunc nec justo erat. Nullam at felis lorem. Vivamus iaculis ac diam a tincidunt. |
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Bcl-2 Selective
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CLL/SLL
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WM
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AML
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ER+/HER2- Breast Cancer
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Solid Tumors
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T-PLL
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Bcl-2/Bcl-xL
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NSCLC + TKI
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MF
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NET
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SummaryPelcitoclax (APG-1252): Dual BCL-2/BCL-xL Inhibitor for Lung Cancer and Other Solid Tumors Pelcitoclax is a novel, highly potent, small molecule designed to restore apoptosis through selective disruption of interaction of antiapoptotic proteins BCL-2 and BCL-xL with proapoptotic proteins such as BIM, etc. This agent has demonstrated reduced platelet toxicity and improved tolerability relative to others of the dual BCL-2 and BCL-xL inhibitor class. Its safety profile as a single agent suggests broad potential as a component of a combination approach to treatment. Pelcitoclax combination treatments are being evaluated for the treatment of lung cancers (small cell lung cancer and non-small cell lung cancer) and has potential in the treatment of specific lymphomas, gastrointestinal tumors, and myelofibrosis. Commercial RightsAscentage retains global rights for commercial development of pelcitoclax. Partnerships |
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MDM2-p53
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Solid Tumors (IO combo)
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AML,MDS
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SummaryAlrizomadlin (APG-115): MDM2-p53 Inhibitor for Solid and Hematologic Malignancies APG-115 is a potent, orally bioavailable MDM2 inhibitor that binds to human recombinant MDM2 protein with high affinity. Mechanistically, APG-115 interferes the binding of MDM2 oncoprotein with the tumor suppressor P53 protein, leads to increased P53 and P21 protein expression and trigger P53-mediated apoptosis. In addition to its direct tumor-targeting activity, APG-115 plays an important role in immune modulation through its effects on immune cells, tumor cells and multiple cytokines. In clinic,, Alrizomadlin monotherapy and combination (i.e., PD-1 blockade) therapy are being developed for the treatment of various solid tumors and hematologic malignancies, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), T-cell prolymphocytic leukemia (T-PLL), and malignant peripheral-nerve sheath tumor (MPNST), advanced solid tumors, as well as other indications. Alrizomadlin has been granted Orphan Drug Designations by the U.S. FDA for the treatment of gastric cancer, soft-tissue sarcoma, AML, Retinoblastoma, IIB-IV melanoma and Neuroblastoma. Impressively, synthetic lethality is achieved by simultaneously triggering both BCL-2-mediated mitochondrial apoptosis by APG-2575 and MDM2-P53 apoptosis by APG-115 in preclinical models of solid and hematologic malignancies. Thus, the combination treatment is able to overcome multiple drug resistance to current therapeutics. Commercial RightsAscentage has global rights, US Clinical Collaboration for Phase II combination trial with pembrolizumab for advance solid tumors. |
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IAP/XIAP
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Solid tumors + IO
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PDAC + Chemo
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HBV
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SummaryAPG-1387: SMAC Mimetic Dimer IAP Antagonist for Solid Tumors and Chronic Hepatitis B Infection APG-1387 is a novel and highly specific small molecule IAP antagonist designed to restore caspase activity and induce apoptosis. APG-1387 as a component of combination therapy with immuno-oncology or chemotherapy treatment has notable potential to improve treatment for solid tumors that have been refractory to multiple prior lines of therapy. This candidate is being evaluated in a combination approach for the treatment of advanced pancreatic cancer. In addition, APG-1387 combination therapy is being evaluated for the treatment of chronic hepatitis B infection. Commercial RightsAscentage has global rights. |
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MM
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MDS
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Candidate Candidate | Molecule Molecule | Condition Condition | Preclinical Pre | Phase I Ph I | Phase II Ph II | Filed Filed | Marketed Mkd |
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EED Selective
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Oncology / Hemoglobinopathy
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SummaryAPG-5918, EED inhibitor for solid and hematologic malignancies APG-5918 is a potent, selective and orally bioavailable EED inhibitor. As an epigenetic modifier, APG-5918 exerts its antitumor activity through allosterically inhibiting H3K27me3 recognition by EED, subsequently inhibiting the methyltransferase activity of polycomb repressive complex 2 (PRC2) and finally derepressing the transcription of tumor suppressor genes. APG-5918 demonstrates excellent antitumor activity in preclinical xenograft models of multiple blood cancers and solid tumors including EZH2 mutant diffuse large B cell lymphoma (DLBCL) and SMARCB1-deficient malignant rhabdoid tumor. APG-5918 is currently under preclinical development for IND filing. Commercial RightsAscentage has global rights |
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Allosteric BCR-ABL
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CML
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SummaryAS1266, BCR-ABL1 allosteric inhibitor for CML AS1266 is an allosteric inhibitor targeting BCR-ABL1, it specifically binds to the myristoyl pocket of BCR-ABL1 protein and inhibits the kinase activity. In ABL1 protein, the pocket is occupied by myristoylated N-terminus resulting in autoinhibition, however, the myristoylated N-terminus is lost in the BCR-ABL1 fusion protein in CML, leading to the constitutive activation of ABL1 kinase. Binding of AS1266 to the myristoyl pocket restores autoinhibition and this novel mechanism is proposed to increase AS1266’s specificity and safety in comparison to current tyrosine kinase inhibitors. In preclinical settings, AS1266 demonstrated significant antiproliferative and antitumor activity in both BCR-ABL1 wild-type and T315I mutant cells and tumor models. |
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Bcl family
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DME
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Commercial RightsAscentage has licensed a library of BCL2 family molecules to Unity for Non-Oncology rights in the US. |
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PROTACs MDM2
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PROTACs MDM2
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Commercial RightsAgreement with the University of Michigan for Global rights. |