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- | NXP800 / Nuvectis Pharma
Journal: NXP800 activates the unfolded protein response, altering AR and E2F function to impact castration-resistant prostate cancer growth. (Pubmed Central) - Mar 17, 2025
Overall, NXP800 has anti-tumor activity against treatment-resistant PCa models, including molecular subtypes with limited treatment options, supporting its consideration for PCa-specific clinical development.
- NXP800 / Nuvectis Pharma, Truqap (capivasertib) / Otsuka, AstraZeneca
ME09. Personalized Molecular Medicine Enabled by Multidisciplinary Approaches to Cancer Drug Discovery and Clinical Development (Location to be announced) - Feb 28, 2025 - Abstract #AACR2025AACR_1628;
Examples will include the AKT inhibitor capivasertib and the developmental GCN2 activator and HSF1 pathway inhibitor NXP800. I will also describe our recent progress towards drugging the transcription factor brachyury, the primary driver of the rare bone cancer chordoma, providing an approach that can be applied to drug other oncogenic transcription factors.
- | cisplatin / Generic mfg., NXP900 / Nuvectis Pharma
Journal: SRC enhanced cisplatin resistance in bladder cancer by reprogramming glycolysis and pentose phosphate pathway. (Pubmed Central) - Jan 12, 2025
eCF506 exhibited excellent anti-tumor effects and effectively enhanced cisplatin-sensitivity. Altogether, our findings demonstrate that targeting SRC is a promising approach to overcome cisplatin-resistance in bladder cancer, and providing new insights for combination therapy in bladder cancer.
- || NXP800 / Nuvectis Pharma
Trial completion date, Trial primary completion date: NXP800-101: A Phase 1 Clinical Study of NXP800 in Subjects with Advanced Cancers and Expansion in Subjects with Ovarian Cancer (clinicaltrials.gov) - Nov 21, 2024
P1, N=61, Recruiting, Sponsor: Nuvectis Pharma, Inc.
Altogether, our findings demonstrate that targeting SRC is a promising approach to overcome cisplatin-resistance in bladder cancer, and providing new insights for combination therapy in bladder cancer. Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> May 2025
- NXP900 / Nuvectis Pharma
A multi-omics approach to identify biomarkers of response to the novel and selective SRC/YES1 inhibitor NXP900 (Exhibition Hall) - Sep 7, 2024 - Abstract #EORTCNCIAACR2024EORTC_NCI_AACR_428;
Unless they are part of the media programme, embargoed or not consented, all abstracts will be released on 9 October 2024. All other abstracts will be released on the day of presentation.
- NXP900 / Nuvectis Pharma
NXP900, a novel YES1/SRC Kinase Inhibitor in Phase 1 Dose Escalation, Demonstrates Potent Synergy with ALK Inhibitors in ALK Resistant Cell Lines (Exhibition Hall) - Sep 7, 2024 - Abstract #EORTCNCIAACR2024EORTC_NCI_AACR_316;
Unless they are part of the media programme, embargoed or not consented, all abstracts will be released on 9 October 2024. All other abstracts will be released on the day of presentation.
- | NXP800 / Nuvectis Pharma
Journal: Gandouling ameliorates liver injury in Wilson's disease through the inhibition of ferroptosis by regulating the HSF1/HSPB1 pathway. (Pubmed Central) - Sep 3, 2024
Importantly, inhibition of this pathway by NXP800 reversed the protective effects of GDL on ferroptosis in the liver of TX mice. In conclusion, GDL shows promise in alleviating liver injury in WD by inhibiting ferroptosis through modulation of the HSF1/HSPB1 pathway, suggesting its potential as a novel therapeutic agent for treating liver ferroptosis in WD.
- | Mekinist (trametinib) / Novartis, BeiGene
Journal: High throughput screening identifies dasatinib as synergistic with trametinib in low grade serous ovarian carcinoma. (Pubmed Central) - Jul 1, 2024
Dasatinib and other SFK inhibitors represent novel candidate treatments for LGSOC and demonstrate synergy with trametinib. Disulfiram represents an additional treatment strategy worthy of investigation.
- | NXP800 / Nuvectis Pharma
Enrollment open: NXP800 for the Treatment of Patients with Advanced or Metastatic Cholangiocarcinoma (clinicaltrials.gov) - Jun 3, 2024
P1, N=30, Recruiting, Sponsor: Mayo Clinic
Disulfiram represents an additional treatment strategy worthy of investigation. Not yet recruiting --> Recruiting
- | NXP800 / Nuvectis Pharma
New P1 trial: NXP800 for the Treatment of Patients with Advanced or Metastatic Cholangiocarcinoma (clinicaltrials.gov) - May 20, 2024
P1, N=30, Not yet recruiting, Sponsor: Mayo Clinic
- NXP800 / Nuvectis Pharma
Discovery of ARID1A loss as a patient biomarker for NXP800 - A developmental activator of the integrated stress response (ISR) and inhibitor of the HSF1 pathway in ovarian cancer (Section 44) - Mar 5, 2024 - Abstract #AACR2024AACR_7698;
P1
We propose that ARID1A loss alters the binding and recruitment of ATF4 and HSF1 leading to the altered and prolonged expression of ATF4 target genes and increased sensitivity to NXP800. NXP800 is currently in phase Ib for the treatment of ARID1A mutant platinum resistant ovarian cancer (NCT05226507).
- NXP800 / Nuvectis Pharma
HSF1 inhibition induces pancreatic ductal adenocarcinoma autophagy through JNK (Section 14) - Mar 5, 2024 - Abstract #AACR2024AACR_7050;
Objective: The objective of this study is to investigate the molecular mechanism of HSF1 inhibition in PDAC autophagy.Methods and In human PDAC cells, Western blotting analysis revealed that HSF1 inhibition via small molecular including CCT361814/NXP800, an HSF1 inhibitor in phase I clinical trials, increased autophagy marker microtubule-associated protein 1A/1B-light chain 3 (LC3) lipidation and decreased expression of phosphorylation of HSF1 at Ser326 and total HSF1 protein, conversely using HSF1 overexpression model reversed this effect... In conclusion, JNK1/2 is involved in HSF1 inhibition-induced PDAC autophagy, targeting autophagy could unveil a novel treatment strategy for pancreatic cancer through targeted HSF1 inhibition.
- NXP800 / Nuvectis Pharma
Pharmacokinetic and pharmacodynamic evaluation of NXP800, a novel GCN2 activator, in a first in human clinical trial (Section 48) - Mar 5, 2024 - Abstract #AACR2024AACR_5182;
In conclusion, JNK1/2 is involved in HSF1 inhibition-induced PDAC autophagy, targeting autophagy could unveil a novel treatment strategy for pancreatic cancer through targeted HSF1 inhibition. Abstract is embargoed at this time.
- NXP800 / Nuvectis Pharma
A novel GCN2 kinase activator demonstrates therapeutic efficacy in preclinical PDX models of human cholangiocarcinoma (Section 29) - Mar 5, 2024 - Abstract #AACR2024AACR_4101;
We are opening a Phase 1b clinical trial investigating the effects of NXP800 use in patients with advanced CCA. Future studies determining the cellular effect of GCN2 activation utilizing NXP800 are being conducted.
- NXP900 / Nuvectis Pharma
NXP900, a novel YES1/SRC kinase inhibitor in phase 1, demonstrates potent inhibition of proliferation in cell lines resistant to ALK and EGFR inhibitors (Section 25) - Mar 5, 2024 - Abstract #AACR2024AACR_2733;
Here we demonstrate that NXP900 can potently inhibit cell proliferation of ALK resistant cell lines as a single agent and EGFR resistant cell lines in combination with osimertinib. Activation of SFK and YAP1 has been shown to be important in the development of resistance to ALK and EGFR treatment.
- NXP900 / Nuvectis Pharma
Src family kinase inhibition demonstrates antitumor activity in vitro and in patient-derived xenograft models of human cholangiocarcinoma (Section 25) - Mar 5, 2024 - Abstract #AACR2024AACR_2732;
We are currently performing multi-omic approaches in NXP900 sensitive and resistant cell lines to unravel determinants of activity and resistance. Additional in vivo studies will be performed to determine effects of NXP900/GemCis and NXP900/anti-PDL-1 combination therapy.
- NXP800 / Nuvectis Pharma
Using acquired resistance to explore the mechanism of action of the integrated stress response/GCN2 activator NXP800 - A new developmental agent for platinum-resistant ARID1A mutant ovarian cancer (Section 21) - Mar 5, 2024 - Abstract #AACR2024AACR_2621;
P1
We have used acquired resistance to understand the MoA of NXP800 as a potent activator of GCN2 and the ISR pathway. Further studies are underway to determine the exact proximal molecular target of NXP800 and the mechanism of GCN2/ISR activation.
- NXP800 / Nuvectis Pharma
A Phase 1b Multicenter, Open-label, Study of NXP800, a Novel GCN2 Kinase Activator, in Patients with Platinum Resistant, ARID1a-mutated Ovarian Cancer (ENGOT-GYN5/NCRI/NXP800-101; GOG-3087) () - Feb 3, 2024 - Abstract #SGO2024SGO_735;
- || NXP900 / Nuvectis Pharma
Enrollment open, Trial initiation date, Metastases: A Phase 1 Clinical Study of NXP900 in Subjects With Advanced Cancers (clinicaltrials.gov) - Oct 5, 2023
P1, N=40, Recruiting, Sponsor: Nuvectis Pharma, Inc.
Further studies are underway to determine the exact proximal molecular target of NXP800 and the mechanism of GCN2/ISR activation. Not yet recruiting --> Recruiting | Initiation date: Jun 2023 --> Oct 2023
- NXP900 / Nuvectis Pharma
NXP900, a novel YES1/SRC kinase inhibitor demonstrates inhibition of YAP1 nuclear localization and potent single agent anti-tumor activity in esophageal squamous cancer models. (LEVEL 2, EXHIBIT HALL D) - Sep 16, 2023 - Abstract #AACRNCIEORTC2023AACR_NCI_EORTC_480;
- NXP800 / Nuvectis Pharma, Cancer Therapeutics CRC
Results of a phase 1 dose escalation clinical trial of NXP800, a novel GCN2 activator, in patients with advanced or metastatic solid tumors. (LEVEL 2, EXHIBIT HALL D) - Sep 16, 2023 - Abstract #AACRNCIEORTC2023AACR_NCI_EORTC_369;
- | Visomitin (plastoquinonyl decyl triphenylphosphonium) / Mitotech, BIO invest, NXP900 / Nuvectis Pharma
Journal: Corneal Edema in Inducible Slc4a11 Knockout Is Initiated by Mitochondrial Superoxide Induced Src Kinase Activation. (Pubmed Central) - Jun 14, 2023
Not yet recruiting --> Recruiting | Initiation date: Jun 2023 --> Oct 2023 Slc4a11 KO-induced CE oxidative stress triggered increased Src kinase activity that resulted in perturbation of the pump components and barrier function of the CE.
- || NXP900 / Nuvectis Pharma
New P1 trial, Metastases: A Phase 1 Clinical Study of NXP900 in Subjects With Advanced Cancers (clinicaltrials.gov) - May 24, 2023
P1, N=40, Not yet recruiting, Sponsor: Nuvectis Pharma, Inc.
- | NXP800 / Nuvectis Pharma, Cancer Therapeutics CRC
Journal: HSF1 Pathway Inhibitor Clinical Candidate (CCT361814/NXP800) Developed from a Phenotypic Screen as a Potential Treatment for Refractory Ovarian Cancer and Other Malignancies. (Pubmed Central) - May 3, 2023
Further multiparameter optimization led to the design of the clinical candidate, CCT361814/NXP800 22, a potent and orally bioavailable fluorobisamide, which caused tumor regression in a human ovarian adenocarcinoma xenograft model with on-pathway biomarker modulation and a clean in vitro safety profile. Following its favorable dose prediction to human, 22 has now progressed to phase 1 clinical trial as a potential future treatment for refractory ovarian cancer and other malignancies.
- NXP900 / Nuvectis Pharma
Preclinical efficacy of NXP900, a YES1/SRC kinase inhibitor in esophageal squamous cancer models. () - Apr 26, 2023 - Abstract #ASCO2023ASCO_4826;
Following its favorable dose prediction to human, 22 has now progressed to phase 1 clinical trial as a potential future treatment for refractory ovarian cancer and other malignancies. In contrast, multi-kinase inhibitors, including dasatinib and bosutinib, block SRC in the active
- |||| NXP800 / Nuvectis Pharma, Cancer Therapeutics CRC
Exciting poster from @ICR_London at #AACR2023 demonstrating activation of the ISR by the HSF1 pathway inhibitor NXP800 presented by @marissavpowers 👍 (Twitter) - Apr 18, 2023
- || NXP800 / Nuvectis Pharma
Enrollment change, Trial completion date, Trial primary completion date: NXP800-101: A Phase 1 Clinical Study of NXP800 in Subjects with Advanced Cancers and Expansion in Subjects with Ovarian Cancer (clinicaltrials.gov) - Apr 14, 2023
P1, N=61, Recruiting, Sponsor: Nuvectis Pharma, Inc.
In contrast, multi-kinase inhibitors, including dasatinib and bosutinib, block SRC in the active N=17 --> 61 | Trial completion date: Apr 2023 --> Jun 2025 | Trial primary completion date: Jan 2023 --> Dec 2024
- NXP800 / Nuvectis Pharma, Cancer Therapeutics CRC
Activation of the integrated stress response by the developmental HSF1 pathway inhibitor NXP800 (Section 34; Poster Board #9) - Mar 14, 2023 - Abstract #AACR2023AACR_6729;
Using an siRNA approach to determine if activation of the ISR components was contributing to growth inhibition following NXP800 exposure, we found that blocking the induction of ATF4 reduced the response of NXP800-sensitive SK-OV-3 human ovarian carcinoma cells to NXP800 treatment.In summary, NXP800 acts on cancer cells to induce activation of the ISR pathway via GCN2, which then leads to inhibition of HSF1 activation. Further studies are underway to determine the precise molecular target of NXP800 and the mechanism of HSF1 pathway inhibition.
- NXP900 / Nuvectis Pharma
In vivo studies demonstrate differences in target inhibition and anticancer efficacy between NXP900 and dasatinib in ovarian clear cell carcinoma model (Section 21; Poster Board #5) - Mar 14, 2023 - Abstract #AACR2023AACR_6220;
NXP900 induces superior target inhibition and anticancer activity than dasatinib in an OCCC xenograft model. The PD study suggests that the conformation selective mode of inhibition of NXP900 is more favorable for clinical development against SFK-driven cancers.
- NXP800 / Nuvectis Pharma, Cancer Therapeutics CRC
Inhibition of HSF1 demonstrates therapeutic efficacy in preclinical models of cholangiocarcinoma (Section 42; Poster Board #14) - Mar 14, 2023 - Abstract #AACR2023AACR_3637;
NXP800, a HSF1 inhibitor, demonstrated significant therapeutic activity in a cholangiocarcinoma PDX. Further studies are needed and being performed to determine the role of HSF1 inhibition in human cholangiocarcinoma.
- NXP800 / Nuvectis Pharma, Cancer Therapeutics CRC
NXP800 versus cisplatin in ARID1a-mutated Ovarian Clear Cell Carcinoma xenograft models (Exhibition and Poster area) - Dec 22, 2022 - Abstract #ESMOGC2023ESMO_GC_37;
P1
Planned phase 1b expansion cohorts will include ovarian clear cell carcinoma and ovarian endometrioid carcinoma patients with ARID1A mutation. Legal entity responsible for the study The authors.
- NXP900 / Nuvectis Pharma
Screening of NXP900 and dasatinib across 121 cancer cell lines identifies differences in their antiproliferative activity profiles (Exhibition Hall) - Sep 3, 2022 - Abstract #AACRNCIEORTC2022AACR_NCI_EORTC_454;
Conclusions Our results indicate that specific patient subgroups may benefit from the distinct pharmacological properties of NXP900, but not from classical FDA-approved type I SRC inhibitors. Further in-depth bioinformatic analysis are ongoing to identify predictive biomarkers associated to NXP900-specific sensitivity to inform the clinical development strategy.
- NXP800 / Nuvectis Pharma, Cancer Therapeutics CRC
Discovery and validation of biomarkers to support clinical development of NXP800: A first-in-class orally active, small-molecule HSF1 pathway inhibitor (Exhibition Hall) - Sep 3, 2022 - Abstract #AACRNCIEORTC2022AACR_NCI_EORTC_252;
P1
Conclusions A Phase 1 trial (NCT05226507) of NXP800 is underway, incorporating the validated predictive, PK and PD biomarkers that constitute a Pharmacological Audit Trail. Future expansion cohorts will include patients with ARID1A mutation, including ovarian clear cell carcinoma and ovarian endometrioid carcinoma.
- || NXP800 / Nuvectis Pharma
FDA event: $NVCT Nuvectis Pharma Announces FDA Clearance of IND for NXP800 https://t.co/kvn0YADWmB (Twitter) - Jun 21, 2022
- NXP800 / Nuvectis Pharma
NXP800: A first-in-class orally active, small-molecule HSF1 pathway inhibitor (La Nouvelle Orleans A-B, Convention Center) - Mar 23, 2022 - Abstract #AACR2022AACR_7985;
Studies to support mechanism of action and identify patient selection biomarkers will be described. A Phase 1 trial of NXP800 is now open, incorporating validated predictive, pharmacokinetic and pharmacodynamic biomarkers that provide a robust Pharmacological Audit Trail and support the prediction of dose-to-human.
- NXP900 / Nuvectis Pharma
Uncovering the molecular mechanisms which predict sensitivity to a novel src kinase inhibitor NXP900 to inform personalized healthcare strategies (Section 26) - Mar 9, 2022 - Abstract #AACR2022AACR_5360;
2021 Nov 1;81(21):5438-5450. doi: 10.1158/0008-5472.CAN-21-0613.
- | NXP800 / Nuvectis Pharma
New P1 trial: NXP800-101: A Phase 1 Clinical Study of NXP800 in Subjects with Advanced Cancers and Expansion in Subjects with Ovarian Cancer (clinicaltrials.gov) - Feb 7, 2022
P1, N=17, Recruiting, Sponsor: Nuvectis Pharma, Inc.
- |||| NXP800 / Nuvectis Pharma
Clinical: 🎉Some lovely news to end the year!Biopharmaceutical company Nuvectis has announced the launch of a new clinical trial of #NXP800, a cancer drug discovered here @ICR_London, led by the fantastic @udai_banerji. Happy New Year! 👩🔬🧑⚕️🔬 https://t.co/v6N0O3wNve (Twitter) - Dec 31, 2021