Nuvectis Pharma Provides Poster Presentation Highlights for NXP900 from the 2025 AACR Meeting

Rhea-AI Summary

Nuvectis Pharma presented key findings for their cancer drug NXP900 at the 2025 AACR Meeting. The Phase 1a dose-escalation study, involving 29 patients with advanced cancers, demonstrated promising results with doses up to 250 mg/day showing an acceptable safety profile.

Key highlights:

• Treatment achieved robust pharmacodynamic responses at tolerated doses
• SRC inhibition exceeded 90% after a single dose
• Most side effects were Grade 1-2, including fatigue and nausea
• Median patient age was 62 years, with 62% males

Three preclinical posters revealed NXP900's potential in NSCLC (non-small cell lung cancer), both as a single agent and in combination with existing therapies. The company plans to commence Phase 1b trials targeting patients with YES1 gene amplifications and hippo pathway alterations, as well as exploring combinations with market-leading therapies for resistant NSCLC.

Positive

• Phase 1a trial shows NXP900 achieved clinically relevant concentrations with 90% SRC inhibition in patient samples
• NXP900 demonstrated acceptable safety profile with mostly Grade 1-2 adverse events
• Drug shows promising preclinical results in NSCLC treatment, both as single agent and combination therapy
• No dose limiting toxicity identified up to 250 mg/day, suggesting good tolerability
• Phase 1b program expansion imminent, targeting specific biomarker-selected cancers

Negative

• Drug still in early clinical stages (Phase 1) with no efficacy data reported yet
• Current trial conducted in 'all-comers' without biomarker selection, limiting effectiveness assessment
• Multiple adverse events reported including fatigue, diarrhea, nausea, and other symptoms

Insights

Oncology Clinical Development Expert

NXP900 shows favorable safety profile with strong target engagement in Phase 1a, supporting upcoming biomarker-driven studies in cancer patients.

The Phase 1a dose-escalation data for NXP900 reveals several encouraging findings from 29 patients with advanced cancers. The drug demonstrated an acceptable safety profile with predominantly Grade 1-2 adverse events including fatigue, diarrhea, and nausea. Importantly, no dose-limiting toxicity was identified even at doses up to 250 mg/day, suggesting a favorable therapeutic window.

The pharmacodynamic data shows robust SRC inhibition exceeding 90% after a single dose, confirming strong target engagement at clinically relevant concentrations starting at 150 mg/day. This molecular validation is critical at this early stage, as it confirms NXP900 is effectively modulating its intended target.

The preclinical data provides clear scientific rationale for the upcoming Phase 1b program, which will pursue two strategic paths: single-agent treatment in biomarker-selected patients with YES1 amplifications and Hippo pathway alterations, and combination therapy with EGFR and ALK inhibitors to address resistance mechanisms in NSCLC.

While these results primarily establish safety rather than efficacy, the pharmacodynamic effect and well-defined biomarker strategy represent meaningful progress. The transition to biomarker-selected cohorts follows contemporary precision oncology principles, potentially increasing the likelihood of demonstrating clinical benefit in Phase 1b expansion.

Biopharma R&D Strategy Expert

NXP900's promising safety data and clear biomarker strategy position Nuvectis for targeted development in precision oncology indications.

Nuvectis's development approach for NXP900 demonstrates strategic sophistication. The completion of the Phase 1a safety assessment while simultaneously gathering pharmacodynamic validation confirms target engagement exceeds 90% at clinically relevant, tolerated doses.

The company's biomarker-guided strategy targeting YES1 amplifications and Hippo pathway alterations represents a scientifically rational approach. Rather than pursuing broad indications, Nuvectis is appropriately focusing on specific molecular segments where mechanistic evidence suggests highest likelihood of benefit.

The dual-track Phase 1b program is particularly noteworthy - pursuing both biomarker-selected monotherapy and strategic combinations to overcome resistance mechanisms in NSCLC. This parallel approach efficiently maximizes potential clinical applications while optimizing development resources.

The preclinical foundation supporting the resistance-reversal strategy in NSCLC provides mechanistic justification for combinations with EGFR and ALK inhibitors. Addressing acquired resistance represents a significant unmet need and potential accelerated development pathway.

While still early-stage, this dataset provides important de-risking information regarding NXP900's safety profile and pharmacological activity. The absence of dose-limiting toxicities at doses up to 250 mg/day, coupled with the clear biomarker-driven plan, increases probability of demonstrating meaningful clinical benefit in subsequent studies.

Phase 1a dose-escalation study data update: treatment with NXP900 resulted in exposure levels leading to robust pharmacodynamic responses across a range of tolerated doses; NXP900 has an acceptable safety profile, dose limiting toxicity dose level has not been identified in doses up to 250 mg/day

Preclinical posters strengthen the NXP900 clinical development strategy as single agent in biomarker-targeted cancers and in combination with market leading therapies to overcome resistance in NSCLC

Fort Lee, NJ, April 29, 2025 (GLOBE NEWSWIRE) -- Nuvectis Pharma, Inc. (NASDAQ: NVCT) ("Nuvectis" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of innovative precision medicines for the treatment of serious conditions of unmet medical need in oncology today provided poster presentation highlights for NXP900 from the 2025 American Association for Cancer Research Meeting (2025 AACR). These posters highlight key data supporting the rationale for the Phase 1b program in biomarker-selected cancers as a single agent, and in combination with market leading therapies to overcome treatment resistance in non-small cell lung cancer (NSCLC). The posters are available on the Company's website.

NXP900 Phase 1a highlights

• 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. Maximal level of SRC inhibition in patient samples after a single dose of NXP900 exceeded 90%.

Three preclinical posters highlight potential use of NXP900 in NSCLC

• 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.

Phase 1b program

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.

Ron Bentsur, Chairman and Chief Executive Officer of Nuvectis commented, “This year’s AACR presentations mark an important milestone in the development of NXP900. As new preclinical data continue to unlock the unique potential of NXP900 as a single agent and as a combination partner, we revealed, for the first time, preliminary clinical data from the ongoing Phase 1a dose escalation clinical trial that provide a link between the existing preclinical mechanistic data and NXP900’s potential in the clinic.” Mr. Bentsur concluded, “with the ability to induce a robust pharmacodynamic response and an acceptable safety profile, we believe that the therapeutic window of NXP900 puts it in a favorable position to demonstrate clinical efficacy in target patients, which is the primary objective of the Phase 1b program that will commence in the coming months. We are excited about the potential of NXP900 as its clinical profile continues to evolve.”

About Nuvectis Pharma, Inc.

Nuvectis Pharma, Inc. is a biopharmaceutical company focused on the development of innovative precision medicines for the treatment of serious conditions of unmet medical need in oncology. The Company is currently developing two clinical-stage drug candidates, NXP800 and NXP900. NXP800 is an oral small molecule GCN2 activator currently in a Phase 1b clinical trial for the treatment for platinum resistant, ARID1a-mutated ovarian carcinoma and in an Investigator-sponsored clinical trial for the treatment of cholangiocarcinoma. NXP900 is an oral small molecule inhibitor of the SRC Family of Kinases (SFK), including SRC and YES1. NXP900's unique mechanism of action enables the inhibition of both the catalytic and scaffolding functions of the SRC kinase thereby providing complete shutdown of the signaling pathway. NXP900 is currently in a Phase 1a dose escalation study.

Forward Looking Statements

This press release contains "forward-looking statements" within the meaning of the federal securities laws, which statements are subject to substantial risks and uncertainties, including statements regarding the expected and intended use of proceeds from the offering. All statements, other than statements of historical facts, contained in this press release are forward-looking statements, including statements regarding the intended. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "aim," "should," "will," "would," or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on Nuvectis Pharma, Inc.'s current expectations, including estimates and projections about future events and trends that we believe may affect our business, financial condition, results of operations, prospects, business strategy, and financial needs. The outcome of the events described in these forward-looking statements are subject to inherent uncertainties, risks, assumptions, market and other conditions, and other factors that are difficult to predict and include statements regarding the preclinical studies for NXP900 and statements regarding NXP900's therapeutic potential and the expected timing for the completion of the Phase 1a dose-escalation study and start of the NXP900 Phase 1b program. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are subject to market and other conditions and described more fully in the section titled "Risk Factors" in our 2024 Form 10-K and our other public filings with the Securities and Exchange Commission ("SEC"). However, these risks are not exhaustive and new risks and uncertainties emerge from time to time, and it is not possible for us to predict all risks and uncertainties that could have an impact on the forward-looking statements contained in this press release or other filings with the SEC. Any forward-looking statements contained in this press release speak only as of the date of this press release. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as may be required by law, and we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995.

Company Contact

Ron Bentsur
Chairman, Chief Executive Officer and President
rbentsur@nuvectis.com

Media Relations Contact

Kevin Gardner
LifeSci Advisors
kgardner@lifesciadvisors.com

FAQ

What are the key findings from Nuvectis (NVCT) NXP900 Phase 1a trial in 2025?

The Phase 1a trial showed NXP900 achieved robust pharmacodynamic responses at tolerated doses, with acceptable safety profile up to 250 mg/day. The drug demonstrated over 90% SRC inhibition in patient samples and showed clinically relevant concentrations starting at 150 mg/day dose.

How effective is NXP900 in treating NSCLC according to AACR 2025 data?

NXP900 showed strong potential in NSCLC treatment by inhibiting YAP1 nuclear localization in YES1/YAP1-amplified NSCLC cells and demonstrated substantial tumor growth inhibition. It also showed ability to reverse resistance when combined with EGFR and ALK kinase inhibitors.

What are the main side effects of Nuvectis NXP900 reported in the 2025 trial?

The most common side effects were primarily Grade 1-2 and included fatigue, diarrhea, nausea, abdominal pain, dyspnea, and vomiting. No dose limiting toxicity was identified up to 250 mg/day.

When will Nuvectis (NVCT) begin Phase 1b trials for NXP900?

Nuvectis plans to commence the Phase 1b trials shortly after concluding the dose escalation phase, focusing on patients with advanced cancers with YES1 gene amplifications and hippo pathway alterations.

What cancers will NXP900 target in Nuvectis Phase 1b trials?

The Phase 1b trials will target advanced cancers with YES1 gene amplifications and hippo pathway alterations, as well as evaluate NXP900 in combination with existing therapies for resistant non-small cell lung cancer (NSCLC).