TRIB3

According to the previous study, NXP-800 caused growth inhibition and regression in various preclinical models, including ARID1A mutated ovarian and endometrial xenograft and cholangiocarcinoma PDX models. On April 5, 2024, the first in human clinical trial of NXP-800 was reported in 2024 AACR. NXP-800's R&D ProgressNXP-800 is a small molecule drug that is being developed in the field of biomedicine. It targets EIF2AK4 x HSF1 and is primarily focused on treating neoplasms, specifically cholangiocarcinoma.  According to the Patsnap Synapse, NXP-800 is currently in the preclinical phase. And the clinical trial distributions for NXP-800 are primarily in the United State and United Kingdom. The key indication is Advanced Malignant Solid Neoplasm.  Detailed Clinical Result of NXP-800This non-randomized, sequential assignment, open-labeled clinical study (NCT05226507)  described the dose-defining dose escalation cohort and the toxicity-pharmacokinetics and pharmacodynamic evaluation in a first-in-human phase I trial of NXP800.   In this study, dose escalation was guided by a Bayesian modified continual reassessment method that targeted a dose-limiting toxicity DLT probability (DLTp) closest to 30% but <33%. Toxicity was assessed using NCI.CTC.V5. Detailed sampling of blood for pharmacokinetic analysis and blood for mRNA and protein analysis in peripheral blood mononuclear cells was conducted on C1D-3 to -7 (run in prior to continuous dosing) and C2D1. Two schedules (once per day [QD] and twice per day [BID] and a dose range of 50 to 150 mg/day were evaluated. The result showed that eighteen patients were treated: at baseline, the median age was 65 years (range 42-77), 9 (50%) were female and 14/18 (78%) had an ECOG score of 1. The most common treatment emergent adverse events (more than 20% of patients) were nausea, vomiting, diarrhea, fatigue, decreased appetite, AST increase and thrombocytopenia. All these side effects were grade 1-2 except grade 3 nausea and grade 3 diarrhea reported in one patient each and grade 3 thrombocytopenia in 2 patients. The MTD for the QD schedule was 100 mg (DLTp=26%), no doses in the BID schedule had estimated DLTp of <33%. The average Cmax at 50 mg and 75 mg OD was 190 nM and 384 nM during the run-in and 495 nM and 656 nM in cycle 2 reached by 3 hours. ATF4 protein in PBMCs was elevated in 57% and 80% of patients during run in and Cycle 2 respectively, 6 hours after 50 mg and 75 mg treatment. The mRNA biomarkers in blood most consistently elevated included ATF4 transcriptional targets NUPR1, ULBP1 and TRIB3 at 2 - 24 hours after 50 mg and 75 mg treatment. Further, mRNA levels for these biomarkers were elevated in post-treatment biopsy samples in one of the two patients tested. It is envisaged that NXP800 will need to be dosed continuously and although the protocol defined MTD at 28 days at 100 mg QD, it was decided to take a dose of range of 50 mg and 75 mg OD which caused biomarker modulation, forward for further evaluation. It can be concluded that a tolerable dose/schedule of continuous dosing of NXP800 has been established with biomarker modulation in blood. Patients will be randomized to two dose levels 50 and 75 mg/day in a QD schedule to evaluate response in a population of ARID1A mutated, platinum-resistant, clear cell ovarian cancer (NCT05226507). How to Easily View the Clinical Results Using Synapse Database?If you want to know the other clinical results of popular conferences, please lick on the “Clinical Results” on the homepage of Patsnap Synapse, which provides multi-dimensional screening and filtering of drugs, indications, targets, companies, result evaluation, release date, popular conferences, etc. to help you quickly locate the data you need.  Select the clinical meeting you are interested in, such as ESMO. In the results, you can quickly locate the data you want to view by indication, phase and drug name.  A single result clearly shows important information such as registration number, phase, indication, Sponsor/Collaborator, biomarker, Trial number, dosing regimen and more.  If you would like to view more information about this result, you can go to the result detail page by clicking on the title.  Above the headings, we provide the original source of the outcome data. The basic information is supplemented with more information beyond the list, such as company, study. design, etc.  In the important Outcome Measures section, we provide both list and flowchart forms, which are convenient for you to overview the comparison group information and core indicator data.  Finally, if you need to download these results, you can conveniently check the check boxes on the left side of the list, or directly click the "Export" button to download the data for personalized analysis and file sharing. Click on the image below to embark on a brand new journey of drug discovery!

Ability Pharmaceuticals announced today that it has received orphan-drug designation (ODD) for ABTL0812 from the US Food and Drug administration (FDA) for the treatment of biliary tract cancer. Barcelona (Catalonia, Spain), November 7, 2018. Ability Pharmaceuticals , a drug development biopharmaceutical company specialized in oncology, announced today that it has received orphan-drug designation (ODD) for ABTL0812 from the US Food and Drug Administration (FDA) for the treatment of biliary tract cancer. The ODD program of the FDA grants special status to medicines and biological products intended to treat, diagnose or prevent rare diseases, which affect fewer than 200,000 people in the USA. This designation establishes a period of exclusivity for seven years of commercialization against competition, as well as certain incentives, such as federal grants, tax credits, a decrease in regulatory fees in the drug approval process, and clinical development advice. The biliary tract refers to the organs and ducts that make, store and release the bile into the small intestine, and includes the liver, gall bladder and bile ducts located inside and outside the liver. Biliary tract cancer is a rare, highly fatal and heterogenous malignancy that arises from different locations within the biliary tree and comprises less than 1% of all human cancers and around 10-15% of all primary liver cancers. It is a life-threatening disease with a significant unmet medical need and treatment options are very limited due to its poor response to chemotherapy, radiation therapy and surgery conventionally used. In preclinical studies, ABTL0812 has shown efficacy in biliary tract cancer as single agent and synergistic effect in combination with taxanes, platinum compounds and gemcitabine, with induction of tumor regression without increasing the toxicity associated with chemotherapy. First-line therapy in patients with biliary tract cancer includes these compounds, and administered in combination with ABTL0812 could greatly improve the treatment outcome. Besides, in the phase 1 study evaluating ABTL8012 as monotherapy with advanced cancer patients, one patient with biliary tract cancer remained stable for 18 months. “We are particularly excited about the opportunity to provide benefit to patients with biliary tract cancer following the outstanding response of one patient that remained stable during 18 months in the phase 1 study with ABTL0812.” said Carles Domenech, PhD, CEO of Ability Pharmaceuticals. “Receiving another orphan designation represents an important milestone as we evaluate to start the clinical program in biliary tract cancer and other cancer types.” About ABTL0812 ABTL0812 is a first-in-class fully differentiated oral targeted anticancer compound causing cell death by autophagy through binding to the nuclear receptors PPARα/γ. It induces TRIB3 overexpression which blocks Akt activation, blocking the Akt/mTOR axis of the PI3K/Akt/mTOR pathway, and induces PPAR-dependent Endoplasmic Reticular Stress (ER-stress). The combination of both effects results in a robust autophagy-mediated cancer cell death. Its unique mechanism of action was published at Clinical Cancer Research in May 2016. In preclinical cancer models ABTL0812 is efficacious as single agent with an excellent safety pro a broad spectrum of cancer types: lung, endometrial and pancreatic cancers, neuroblastoma and glioma. In these models the compound has also synergistic effect with chemotherapy (taxanes, platinum compounds and gemcitabine) without increasing its toxicity. In Europe, ABTL0812 is currently in phase 2 as first line therapy in combination with chemotherapy in patients with endometrial or squamous lung cancer. The study includes centers in Spain and France. The Investigational New Drug (IND) for endometrial cancer or squamous non-small cell lung cancer was approved by the US FDA in December 2017, followed by the approval of a phase 1/2 pancreatic cancer study one month later. Also, ABTL0812 has been granted the Orphan Drug Designation (ODD) for neuroblastoma and pancreatic cancer by the FDA in the US and by the EMA in Europe. In the phase 1/1b clinical trial (29 patients with advanced solid tumors), ABTL0812 showed the best safety and tolerability compared to other inhibitors of the pathway; no dose-limiting toxicities were identified. The efficacy in patients was comparable to the best PI3K/Akt/mTOR inhibitors in similar clinical trials. Remarkably 2 patients had extremely long disease stabilizations over one year (14 and 18 months). Additionally, ABTL0812 showed high efficacy on biomarkers of the pathway with dose-response effect. About Ability Pharmaceuticals Ability Pharmaceuticals ( ) is a clinical-stage biopharmaceutical company focused on creating the future of oncology by developing innovative therapies that address unmet medical needs. The company was established in 2009 with two drug candidates in development: ABTL0812, a targeted therapy already in phase 2 clinical trials and ABTL0815 in preclinical development. In April 2016, AbilityPharma signed a territorial license agreement for ABTL0812 with the NASDAQ US company SciClone Pharmaceuticals, Inc. to develop and market the product in Greater China. Ability Pharmaceuticals has headquarters in Cerdanyola del Vallès (Barcelona, Catalonia, Spain) at Parc Tecnològic del Vallès and Parc de Recerca UAB. Current shareholders include the biotech venture firms Inveready and SODENA, its founders and private investors, and has the financial support from ACCIO (Government of Catalonia), CDTI, ENISA and MINECO (Government of Spain). AbilityPharma has launched a financial round of 3-5M euros which includes a 1M euros crowdfunding campaign with Capital Cell. campaign/ability- pharmaceuticals/ Contact information: Carles Domènech, PhD CEO Ability Pharmaceuticals email: media.relations@abilitypharma. com Tel.: +34 935 824 411