NXP900 / Nuvectis Pharma - LARVOL DELTA

Yes/src kinase inhibitor nxp900, currently in clinical development, combines synergistically with fulvestrant against luminal a breast cancer cell lines in vitro and in vivo (SABCS 2025) - "Dose response studies were performed for NXP900, dasatinib and fulvestrant in a library of ER+ luminal A cell lines. Our results demonstrate that luminal A cancer cell lines are generally sensitive to NXP900 treatment and that in combination with endocrine therapy it is more synergistic than the standard-of-care combination of fulvestrant and CDK4/6 inhibitors. This study supports the potential translation of NXP900 into breast cancer patients alongside endocrine therapies to improve the treatment of ER+ tumors."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • FAT1 • HER-2 • YAP1

Characterisation of Src-family kinase inhibitors in lung fibroblasts shows distinct signalling complexes required for matrix synthesis and differentiation (BTS WM 2025) - "While less selective compounds showed inhibition of both processes, a novel, more selective and conformation-dependent inhibitor (NXP900) showed only inhibition of α-SMA expression, suggesting independent mechanisms for these processes. Cell-free kinome scan assays and cell-based phosphoproteomics revealed that more selective SFK inhibition does not affect TGF-β1-mediated mTOR signalling required for ECM synthesis, but does modulate cell signalling complexes associated with cytoskeletal organisation, focal adhesion, and cell-cell/substrate junctions. These results suggest specific roles for the SFKs in myofibroblast differentiation with implications for therapeutically targeting functional heterogeneity in pathological cell sub-populations in IPF."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • TGFB1

Nuvectis Pharma to Host a Virtual Key Opinion Leader Meeting to Discuss the NXP900 Phase 1b Program in Advanced Solid Tumors, Including the Combination with Osimertinib in NSCLC (GlobeNewswire) - "Event scheduled for Tuesday, December 2nd at 8:00 AM ET....The discussion will focus on key NXP900 preclinical and clinical data to date and the strategy for the monotherapy and combination components of the NXP900 Phase 1b clinical program."

Clinical data • Preclinical • Non Small Cell Lung Cancer

Dual targeting of RET and SRC synergizes in RET fusion-positive cancer cells. (PubMed, Mol Oncol) - "Our results show that the multitargeted SRC TKI dasatinib significantly enhanced the efficacy of RET TKIs in RET fusion-positive (RET+) NSCLC and PTC cells...Importantly, synergy was also observed with eCF506 (NXP900), a next-generation clinical SRC inhibitor. Finally, both SRC TKIs restored sensitivity in selpercatinib-resistant RET+ PTC cells. These results elucidate RET and SRC signaling crosstalk in RET+ NSCLC and PTC, suggesting that co-inhibiting SRC has clinical potential in TKI-naïve and -resistant RET+ cancers."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • RET • RPS6

Clinical safety, pharmacokinetics, pharmacodynamics, and cytochrome P450 interactions for the SRC/YES1 kinase inhibitor NXP900 (AACR-NCI-EORTC 2025) - P1 | "In combination, the addition of NXP900 to lorlatinib or osimertinib resulted in synergistic inhibition of cell proliferation in lorlatinib and osimertinib-resistant NSCLC cell lines. The advancement of NXP900 into the next development stage is supported by its emerging clinical profile, including acceptable safety, robust PD response in clinically relevant doses and weak interactions with key CYP enzymes. A phase 1b study of NXP900 as monotherapy in patients with advanced solid tumors with specific genomic alterations is ongoing (NCT05873686)."

Clinical • Late-breaking abstract • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CYP1A2 • YES1

NXP900, a novel YES1/SRC kinase inhibitor currently in clinical development, potently inhibits tumor growth in FAT1 mutated xenograft models (AACR-NCI-EORTC 2025) - "Conversely, multi-kinase inhibitors dasatinib and bosutinib target the "open' conformation (type 1), thus promoting SFK association with signalling partners and as a consequence inducing a paradoxical enhancement of SFK activity as the inhibitor's dissociates from the ATP site2. NXP900 prevents YAP1 nuclear localization and inhibits SRC phosphorylation at concentrations that have been demonstrated to be clinically achievable in plasma and well tolerated in a phase 1 dose escalation study. Our data suggests that NXP900 has therapeutic potential as single agent in FAT1 mutated cancers. A Phase1b expansion study in patients with FAT1 and other genomic alterations in solid tumors is ongoing."

Preclinical • Lung Cancer • Oncology • Solid Tumor • CDH1 • CDH23 • FAT1 • PCDH • TAFAZZIN • YAP1

Nuvectis Pharma Announces Upcoming Presentations for NXP900 at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire)

Clinical data • Preclinical • Oncology

Characterisation of Src-family kinase inhibitors in lung fibroblasts shows distinct signalling complexes required for matrix synthesis and differentiation (ERS 2025) - "While less selective compounds showed inhibition of both processes, a novel, more selective inhibitor (NXP900) showed only inhibition of α-SMA expression, suggesting independent mechanisms for these processes. Cell-free kinome scan assays and cell-based phosphoproteomics revealed that more selective SFK inhibition does not affect TGF-β1-mediated mTOR signalling required for ECM synthesis, but does modulate cell signalling complexes associated with cytoskeletal organisation, focal adhesion, and cell-cell/substrate junctions. These results suggest specific roles for the SFKs in myofibroblast differentiation with implications for therapeutically targeting functional heterogeneity in pathological fibroblast sub-populations in IPF."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • TGFB1

NXP900-101: A Phase 1 Clinical Study of NXP900 in Subjects With Advanced Cancers (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Nuvectis Pharma, Inc. | N=40 ➔ 140 | Trial completion date: May 2025 ➔ Jul 2027 | Trial primary completion date: Apr 2025 ➔ Mar 2027

Enrollment change • Trial completion date • Trial primary completion date • Kidney Cancer • Lung Adenocarcinoma • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma

Nuvectis Pharma Announces the Initiation of the Phase 1b Program for NXP900 (GlobeNewswire) - "The Phase 1b program is designed to evaluate the clinical activity of NXP900 as a single agent in patients with advanced solid tumors whose cancers harbor specific genetic alterations, and in combination with EGFR and ALK inhibitors in patients with NSCLC whose cancers developed resistance to these treatments."

Trial status • Solid Tumor

Nuvectis Pharma…Reports Completion of the NXP900 Phase 1a Dose Escalation Study (GlobeNewswire) - "With the recent successful completion of the NXP900 DDI study, which supports the potential combination of NXP900 with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors in non-small cell lung cancer (NSCLC), and now the successful completion of the Phase 1a dose-escalation study, the Company is poised for the start of the Phase 1b study of NXP900, expected in the coming weeks....The final data from the study is expected to be presented at a future medical/scientific conference."

P1 data • Trial completion • Non Small Cell Lung Cancer • Solid Tumor

Nuvectis Pharma, Inc. Reports First Quarter 2025 Financial Results and Business Highlights (GlobeNewswire) - "On the NXP800 side, enrollment into the Phase 1b study in patients with platinum resistant, ARID1a mutated ovarian cancer continues, and we expect to provide an update from this study in a couple of months....We are excited about the upcoming months with NXP900 entering the Phase 1b portion of its clinical development and believe that with the recent financing we have working capital to take us through key clinical development milestones and into 2027.”"

Platinum resistant • Trial status • Endometrioid Carcinoma • Ovarian Cancer

NXP900 Phase 1a highlights (GlobeNewswire) - P1a | N=40 | NCT05873686 | Sponsor: Nuvectis Pharma, Inc. | Twenty-nine patients with advanced cancers (not selected for target biomarkers, i.e., 'all comers') were treated with single agent NXP900 at doses ranging from 20 to 250 mg/day. In these patients, the median age was 62 years (range: 36-89), 62% were males, 83% had an ECOG performance score of 1, and the median number of prior therapies was 5. The most common treatment emergent adverse events were fatigue, diarrhea, nausea, abdominal pain, dyspnea and vomiting, mostly reported as Grade 1-2. The dose limiting toxicity (DLT) dose level has not been identified in doses up to 250 mg/day. Systemic exposure increased with increased doses of NXP900, achieving clinically relevant concentrations starting at the 150 mg/day dose, as demonstrated by a robust pharmacodynamic response."

P1 data • Solid Tumor

Three preclinical posters highlight potential use of NXP900 in NSCLC (GlobeNewswire) - "As a single agent, NXP900 potently inhibited YAP1 nuclear localization and the proliferation of YES1/YAP1-amplified NSCLC cells in vitro and induced substantial tumor growth inhibition in an in vivo model of YES1-amplified NSCLC. Together, these are the data that demonstrate the relevance of inhibiting NXP900’s direct target, the SRC kinase family member YES1, in NSCLC, and provide the rationale to target NSCLC and potentially other cancers with Hippo pathway inactivating alterations (YAP1, FAT1, NF2, TAZ). As a combination partner, the addition of NXP900 to market leading epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) kinase inhibitors resulted in reversal of resistance to the anti-EGFR and anti-ALK agents, providing the scientific rationale for the clinical development of NXP900 in these settings, as acquired resistance remains an unmet clinical need in NSCLC."

Preclinical • Non Small Cell Lung Cancer

Phase 1b program (GlobeNewswire) - "The Phase 1b portion of the single agent study is expected to commence shortly after the conclusion of the dose escalation phase, in which patients with advanced cancers with YES1 gene amplifications and hippo pathway alterations will be included. Another objective of the Phase 1b program is to evaluate NXP900 in combination with existing market-leading therapies for the treatment of resistant NSCLC."

New trial • Non Small Cell Lung Cancer

NXP900, a novel YES1/SRC kinase inhibitor currently in clinical development, blocks YAP1 signaling in NSCLC cell lines (AACR 2025) - "Conversely, multi-kinase inhibitors dasatinib and bosutinib target the "open" conformation (type 1), thus promoting SFK association with signalling partners3. NXP900 prevents YAP1 nuclear localization and cell cycle progression in a panel of NSCLC cell lines, decreasing expression of total YAP1 and YES1. Our data suggests that NXP900, currently in a Phase1 dose escalation study, is an attractive and translatable combination partner that could synergize with existing targeted therapies against NSCLC when the Hippo pathway is dysregulated."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • YAP1

Multiomic profiling identified biomarkers of response to selective Src family kinase inhibition in preclinical models of cholangiocarcinoma (AACR 2025) - "NXP900 is a highly selective SFK inhibitor a novel mechanism of action that locks SFKs in a closed, inhibited conformation, preventing interaction with substrate proteins, unlike other SFK inhibitors like dasatinib. This study identified molecular markers linked to response to SFK inhibition, which could be utilized for patient selection for NXP900 treatment. Further studies are validating these findings and exploring combination therapies to address resistance mechanisms."

Preclinical • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • EGFR • LYN • SYK

NXP900, a phase 1, first-in-class YES1/SRC inhibitor demonstrates potent single agent activity and synergy with ALK inhibitors in ALK resistant NSCLC models (AACR 2025) - "In contrast, multi-kinase inhibitors, including dasatinib and bosutinib, lock SRC in the active "open" conformation (type 1 inhibitors) promoting the association of SFK and signaling partners via allosteric facilitation (Higuchi et al. Despite high response rates to lorlatinib and long duration of response, acquired resistance almost universally arises. Here we demonstrate that NXP900 can potently inhibit cell proliferation of ALK resistant cell lines as a single agent and is synergistic with lorlatinib in NSCLC models harboring different variants of the ALK gene fusion. Altogether, these data suggest that NXP900 may have therapeutic potential in cancers with acquired resistance to ALK inhibitors."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4

Overcoming osimertinib resistance in NSCLC with NXP900, a phase 1, highly selective and potent first-in-class total YES1/SRC inhibitor (AACR 2025) - "In contrast, multi-kinase inhibitors, including dasatinib and bosutinib, block SRC in the active "open" conformation (type 1 inhibitors) promoting the association of SFK and signaling partners via allosteric facilitation (Higuchi et al. Despite high response rates to osimertinib in EGFR mutant lung cancer patients acquired resistance almost universally arises. Here we demonstrate that NXP900 in combination with osimertinib demonstrates potent synergy and prolonged inhibition of tumor growth in in vitro and in vivo NSCLC models of acquired osimertinib resistance. Altogether, these data suggest that NXP900 may have therapeutic potential in EGFR mutant cancers with acquired resistance to osimertinib."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

First in human phase 1 trial of the SRC family kinase inhibitor NXP900 in patients with advanced solid tumors (AACR 2025) - P1 | "In its first-in-human clinical trial in patients with advanced solid tumors NXP900 was biologically active with an acceptable safety profile, supporting its continued clinical development."

Clinical • Metastases • P1 data • Oncology • Solid Tumor

Endocrine therapy-resistant luminal A breast cancer cell lines are sensitive to the novel YES1/SRC tyrosine kinase inhibitor, NXP900 (AACR 2025) - "Recent findings using ER+ cell lines show increased sensitivity with NXP900 as opposed to other kinase inhibitors, such as dasatinib or bosutinib. Additionally, our longitudinal data suggests that NXP900 is a strong therapeutic candidate to treat ER+ cell lines with acquired endocrine resistance. This study supports the potential translation of NXP900 into an adjuvant clinical setting, alongside endocrine therapies, to improve breast cancer treatment in patients with ER+ tumors."

Late-breaking abstract • Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER

Nuvectis Pharma Announces Upcoming Presentations for NXP900 at the 2025 American Association for Cancer Research Meeting (GlobeNewswire) - "Nuvectis Pharma, Inc...announced upcoming presentations for NXP900 at the upcoming 2025 American Association for Cancer Research Meeting (2025 AACR), taking place from April 25th to April 30th in Chicago, IL."

Preclinical • Breast Cancer • Non Small Cell Lung Cancer • Solid Tumor

Nuvectis Pharma Announces a New Publication of a Research Study Demonstrating that the Combination of NXP900 and EGFR Inhibitors Improves the Efficacy of the EGFR Inhibitors in Preclinical Models of EGFR Mutated NSCLC (GlobeNewswire) - "Nuvectis Pharma...announced a new publication from the laboratory of Prof. Ruth Keri, (Cleveland Clinic, Cleveland, OH, USA) demonstrating that the combination of NXP900 and osimertinib (the active ingredient in Tagrisso) was superior to single agent osimertinib in vivo in a model of Epidermal Growth Factor Receptor(EGFR) mutated non-small cell lung cancer (NSCLC), and led to decreased cell proliferation and increased apoptosis in vitro. The data reported in this new publication (Cuellar-Vite et al., Molecular Cancer Research, 2025; DOI: 10.1158/1541-7786.MCR-24-030) further supports the mechanistic rationale for the combination of NXP900 and EGFR inhibitors in EGFR-mutated tumors, and further validates the data previously published by the research team at Astra Zeneca which demonstrated that the addition of NXP900 to osimertinib reverses resistance to osimertinib in osimertinib resistant cell lines."

Preclinical • Non Small Cell Lung Cancer

Nuvectis Pharma, Inc. Reports 2024 Financial Results and Business Highlights (GlobeNewswire) - "NXP800 Phase 1b study in patients with platinum resistant, ARID1a-mutated ovarian cancer is ongoing...NXP900 Phase 1a dose escalation study continues to enroll, preparation for the start of the Phase 1b program is underway. Phase 1b program expected to begin in mid-2025....'Enrollment is ongoing in the Phase 1b clinical trial, in which patients with platinum resistant, ARID1a-mutated ovarian cancer are currently being treated with a dose of 75mg/day, on an intermittent dosing schedule. We intend to provide an update from this study in the second quarter and plan to provide the first data from the investigator-initiated study in cholangiocarcinoma later this year.'"

Enrollment status • New P1 trial • P1 data • Cholangiocarcinoma • Ovarian Cancer

NXP900-101: A Phase 1 Clinical Study of NXP900 in Subjects with Advanced Cancers (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Nuvectis Pharma, Inc. | Trial primary completion date: Jan 2025 ➔ Apr 2025

Trial primary completion date • Oncology • Solid Tumor