Delving into the Latest Updates on NP-G2-044 with Synapse

Fascin is an actin-binding protein that promotes tumor metastasis. The inhibition of fascin on the progress of non-small cell lung cancer (NSCLC) is not very clear. Hence, this study explored the potential effect of NP-G2-044, a novel fascin inhibitor, in human NSCLC lines and the Lewis lung cancer (LCC) mice model.

Methods::

The growth of cells was analyzed via CCK-8 assays, and the flow cytometry was adopted for cell cycle and apoptosis analysis, as well as the migration and invasion of NSCLC cells with or without NP-G2-044. The therapy of NP-G2-044, which synergizes with cisplatin and PD-1, was evaluated in the established xenograft Lewis’s lung cancer of mice.

Results::

Fascin was overexpressed in human NSCLC cells, and inhibition of fascin by NP-G2-044 attenuated NSCLC cell growth and remarkably undermined the ability of migration and invasion in vitro, which was related to the reduced epithelialmesenchymal transition (EMT) including downregulation of N-cadherin and vimentin, and upregulation of E-cadherin. Further results implied that the above changes may be partially mediated by the Wnt/β-catenin pathway. In vivo, NP-G2-044 slowed down tumor development and enhanced overall survival alone, leading to synergistic anticancer effects with cisplatin or PD-1 inhibitor.

Conclusion::

Fascin inhibition could inhibit the metastasis of NSCLC and has the potential to enhance the efficacy of cisplatin and PD-1 inhibitors by blocking the Wnt/β- catenin pathway.

01 May 2024·The Journal of pathology

KAT8/SIRT7‐mediated Fascin‐K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma

Article

Author: Dong, Geng ; Wen, Bing ; Xu, Xiu-E ; Zhao, Hui ; Li, En-Min ; Wu, Jian-Yi ; Xu, Li-Yan ; Wang, Shao-Hong ; Shi, Wen-Qi ; Liao, Lian-Di ; Zhang, Zhi-Da ; Guo, Zhen-Chang ; Zhong, Jin-Ling ; Wu, Zhi-Yong ; Zhang, Kai ; Li, Da-Jia ; Pan, Jin-Mei ; Cheng, Yin-Wei ; Nie, Ping-Juan ; Huang, Qing-Feng

Abstract:

Fascin actin‐bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F‐actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin‐mediated F‐actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD‐dependent protein deacetylase sirtuin (SIRT) 7‐mediated deacetylation of Fascin‐K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin‐K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin‐K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP‐G2‐044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP‐G2‐044 may be more suitable for patients with low levels of Fascin‐K41 acetylation, but not suitable for patients with high levels of Fascin‐K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

01 Jan 2023·Technology in cancer research & treatment

The Role of Fascin-1 in Human Urologic Cancers: A Promising Biomarker or Therapeutic Target?

Review

Author: Ma, Xiaolei ; Gao, Yankun ; Li, Xiangling ; Bian, Qiang ; Zhao, Zhankui ; Wang, Qianqian ; Shi, Ying ; Yu, Honglian ; Chen, Huiyuan ; Zhang, Naibin

Human cancer statistics show that an increased incidence of urologic cancers such as bladder cancer, prostate cancer, and renal cell carcinoma. Due to the lack of early markers and effective therapeutic targets, their prognosis is poor. Fascin-1 is an actin-binding protein, which functions in the formation of cell protrusions by cross-linking with actin filaments. Studies have found that fascin-1 expression is elevated in most human cancers and is related to outcomes such as neoplasm metastasis, reduced survival, and increased aggressiveness. Fascin-1 has been considered as a potential therapeutic target for urologic cancers, but there is no comprehensive review to evaluate these studies. This review aimed to provide an enhanced literature review, outline, and summarize the mechanism of fascin-1 in urologic cancers and discuss the therapeutic potential of fascin-1 and the possibility of its use as a potential marker. We also focused on the correlation between the overexpression of fascin-1 and clinicopathological parameters. Mechanistically, fascin-1 is regulated by several regulators and signaling pathways (such as long noncoding RNA, microRNA, c-Jun N-terminal kinase, and extracellular regulated protein kinases). The overexpression of fascin-1 is related to clinicopathologic parameters such as pathological stage, bone or lymph node metastasis, and reduced disease-free survival. Several fascin-1 inhibitors (G2, NP-G2-044) have been evaluated in vitro and in preclinical models. The study proved the promising potential of fascin-1 as a newly developing biomarker and a potential therapeutic target that needs further investigation. The data also highlight the inadequacy of fascin-1 to serve as a novel biomarker for prostate cancer.

1

News (Medical) associated with NP-G2-044

13 Feb 2025

·www.prnewswire.com

Novita to Present Additional Data from Phase 2 Trial of NP-G2-044 in Patients with Advanced and Metastatic Solid Tumors at American Association for Cancer Research Immuno-Oncology Conference 2025 (AACR IO) Annual Meeting

NEW YORK, Feb. 13, 2025 /PRNewswire/ -- Novita Pharmaceuticals, Inc., a privately held, clinical-stage pharmaceutical company dedicated to developing novel cancer drugs through its proprietary fascin inhibitor technology, today announced that the Company will present additional data from the Phase 2 trial of its novel fascin inhibitor, NP-G2-044, at the American Association for Cancer Research Immuno-Oncology Conference 2025 (AACR IO), being held February 23-26, 2025 in Los Angeles, California. Details of the poster presentation are below. Title: Phase 2 Study of NP-G2-044, a Novel Fascin Inhibitor, in Combination with Anti-PD-1 Therapy in Patients with Solid Tumors Resistant to Prior Anti-PD-1 Therapy Session: Poster Session B Date and Time: Tuesday, February 25, 2025 at 1:45-4:00 p.m. PT Presenting Author: Anup Kasi, M.D., M.P.H., University of Kansas Medical Center The poster will be available on Novita's website following the presentation. For more details about the AACR IO Annual Meeting, please visit their website here. About Novita's Pioneering Research in Fascin Inhibition Cancer metastasis is the primary cause of over 90% of cancer-related deaths, yet there is currently no drug on the market specifically targeting metastasis. Furthermore, while Immuno-Oncology (IO) therapies, particularly immune checkpoint inhibitors, have made significant strides in cancer treatment, a large proportion of patients do not respond to existing IO treatments. Novita aims to address both of these critical medical needs by developing fascin inhibitors, which target a key protein involved in tumor cell motility and highly expressed in tumor cells and antigen-presenting cells within tumor tissues. The Company's lead asset, NP-G2-044, is a small-molecule fascin inhibitor that has demonstrated the ability to block metastasis in both preclinical and clinical studies. Additionally, when combined with immune checkpoint inhibitors, NP-G2-044 has shown potential to reinvigorate anti-tumor immune responses. Novita's multicenter Phase 2 clinical trial, titled "NP-G2-044 as Monotherapy and Combination Therapy in Patients with Advanced or Metastatic Solid Tumor Malignancies," is currently ongoing and approaching completion. About Novita Novita Pharmaceuticals, Inc. ("Novita" or the "Company") is a privately held, clinical-stage biopharmaceutical company focused on developing groundbreaking therapies using its proprietary fascin inhibitor technology to prevent and treat cancer metastasis while simultaneously enhancing anti-cancer immune responses. For more information, visit . Media Contact: Argot Partners (media) David Rosen 212.600.1902 [email protected] Investor Contact: Argot Partners (investors) Noor Pahlavi 212.600.1902 [email protected] SOURCE Novita Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2ImmunotherapyAACR

100 Deals associated with NP-G2-044

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Esophageal Squamous Cell Carcinoma	Phase 2	US	Novita Pharmaceuticals, Inc.	07 Dec 2021
Non-Muscle Invasive Bladder Neoplasms	Phase 2	US	Novita Pharmaceuticals, Inc.	07 Dec 2021
Pancreatic Ductal Adenocarcinoma	Phase 2	US	Novita Pharmaceuticals, Inc.	07 Dec 2021
Platinum-Resistant Ovarian Carcinoma	Phase 2	US	Novita Pharmaceuticals, Inc.	07 Dec 2021
Squamous Cell Carcinoma of the Oropharynx	Phase 2	US	Novita Pharmaceuticals, Inc.	07 Dec 2021
Triple Negative Breast Cancer	Phase 2	US	Novita Pharmaceuticals, Inc.	07 Dec 2021
Liver Cancer	Phase 1	US	Novita Pharmaceuticals, Inc.	21 Dec 2017
Ovarian Cancer	Phase 1	US	Novita Pharmaceuticals, Inc.	21 Dec 2017
Prostatic Cancer	Phase 1	US	Novita Pharmaceuticals, Inc.	21 Dec 2017
Colonic Cancer	Phase 1	US	TGen Drug Development Services	03 Nov 2017

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03199586 (ASCO 12021 \| ASCO 22021) Manual	Phase 1	Metastatic Solid Tumor \| Neoplasms	23	NP G2 044	hfxqjmasqx(ipvmgxrapq) = dsfufnypka lanjjxlwou (lopskhvdci ) View more	Positive	20 May 2021
				NP G2 044 (Ovary + Last Prior Therapy:CSF1R Inhibitor)	nsfrynsyyp(dalediwuge) = lrdlqoyglq pfnicjestb (kvwbbontdo )