NP-G2-044 / Novita Pharma, Protheragen, CR Double-Crane - LARVOL DELTA

Durable responses in ICI-refractory or acquired resistance: Phase 2 study of NP-G2-044 combined with anti-PD-1 therapy. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT05023486 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

P2 data • Preclinical

Novita Pharmaceuticals Announces Oral Presentation of Phase 2 NP-G2-044 Data at the 2025 American Society for Clinical Oncology (ASCO) Annual Meeting (PRNewswire) - "Novita Pharmaceuticals...announced that additional data from its Phase 2 Study of NP-G2-044 combined with anti-PD-1 therapy will be presented in an oral presentation as part of a Rapid Oral Session at the 2025 American Society for Clinical Oncology (ASCO) Annual Meeting..."

P2 data • Solid Tumor

A Study of DC05F01 in Chinese Patients with Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: Heronova Pharmaceuticals

New P1 trial • Oncology • Solid Tumor

A Study of DC05F01 in Chinese Patients with Recurrent/Refractory Ovarian Cancer and Other Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: Heronova Pharmaceuticals

New P1/2 trial • Lung Cancer • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor

Novita Presents Additional Positive Data from Phase 2 Trial of NP-G2-044 in Patients with Advanced and Metastatic Solid Tumors at AACR IO Annual Meeting (PRNewswire) - P1/2 | N=140 | NCT05023486 | Sponsor: Novita Pharmaceuticals, Inc. | Key highlights include: A Disease Control Rate of 76% (includes patients with Stable Disease and Objective Responses); An ORR of 21% (95% CL 9-38.9%) including 4 patients with Partial Response (PR) and 3 patients with Complete Responses (CR) including Pathologic Complete Response...; Notable outcomes include a CR in a cervical cancer patient, target lesion CR in an endometrial cancer patient, pathological CRs in a pancreatic cancer patient and a patient with gastroesophageal junction adenocarcinoma and PRs in cutaneous squamous cell carcinoma, non-small cell lung cancer, and cholangiocarcinoma....We look forward to sharing additional data from the Phase 2 expansion cohort of NP-G2-044 in combination with ICI in the second half of 2025....Novita is on track to begin enrollment in its pivotal Phase 3 study of NP-G2-044 + PLD in platinum resistant ovarian cancer in the third quarter of 2025."

New P3 trial • P2 data • Cervical Cancer • Cholangiocarcinoma • Endometrial Cancer • Gastroesophageal Junction Adenocarcinoma • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Cancer • Squamous Cell Skin Cancer

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 (PRNewswire) - "Novita Pharmaceuticals...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."

P2 data • Solid Tumor

NP-G2-044 as Monotherapy and Combination Therapy in Patients With Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2 | N=140 | Recruiting | Sponsor: Novita Pharmaceuticals, Inc. | N=100 ➔ 140

Enrollment change • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Vaginal Cancer • EGFR

Fascin Inhibitor NP-G2-044 Decreases Cell Metastasis and Increases Overall Survival of Mice-Bearing Lung Cancers. (PubMed, Curr Mol Med) - "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."

Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDH1 • CDH2 • Fascin • VIM

NP-G2-044 As Monotherapy and Combination Therapy in Patients with Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Novita Pharmaceuticals, Inc. | Trial completion date: Sep 2024 ➔ Sep 2025 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Vaginal Cancer • EGFR

Thymic stromal lymphopoietin contributes to airway responses to ozone via dendritic cells (ERS 2024) - "Clodronate was treated to deplete dendritic cell and NP-G2-044 was administrated to inhibit fascin. Conclusion TSLP is crucial for ozone-induced AHR and neutrophilic airway inflammation via DCs. As the mechanisms, fascin derived from cDC1 is associated with neutrophilic airway inflammation (Fig 2D)."

Stroma • Asthma • Immunology • Inflammation • Respiratory Diseases • CRLF2 • Fascin • FSCN1 • TSLP

Targeting Fascin1 maintains chondrocytes phenotype and attenuates osteoarthritis development. (PubMed, Bone Res) - "Moreover, FSCN1 inhibitor NP-G2-044 effectively reduced extracellular matrix degradation in OA mice, cultured human OA chondrocytes, and cartilage explants by suppressing ALK1/Smad1/5 signaling. These findings suggest that targeting FSCN1 represents a promising therapeutic approach for OA."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • ALK1 • Fascin • FSCN1 • TGFB1

A phase 2 clinical trial of first-in-class fascin inhibitor NP-G2-044 as monotherapy and in combination therapy with anti-PD-1 immunotherapy in patients with advanced solid tumor malignancies. (ASCO 2024) - P1/2 | "The first-in-class fascin inhibitor, NP-G2-044, appears safe and well tolerated administered both as MT and in CT with IO. Signals of anti-cancer and anti-metastatic activity were observed with both mono and combination therapy. A phase 3 randomized clinical trial evaluating NP-G2-044 in combination with chemo in pts."

Clinical • Combination therapy • Metastases • Monotherapy • P2 data • Fatigue • Gynecologic Cancers • Non-melanoma Skin Cancer • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Fascin • FSCN1

Fascin1 might be a promising molecular target for colorectal cancer patients at advanced stage (AACR 2024) - "Using two human CMS4-CRC cell lines, SW480 and HCT116, we investigated the effects of the fascin-1 inhibitors, NP-G2-044 and BDP-13176, on the proliferation and the migration activity of CMS4-CRC cells via MTT assay and a wound-healing assay. Fascin-1 is expressed both on cancer cells and on stromal cells, but mainly expressed on cancer cells... Fascin-1 is one of key molecules for the development of CRC. Fascin-1 might be a promising molecular target for CMS4-CRC patients at advanced stage."

Clinical • Metastases • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • Fascin

KAT8/SIRT7-mediated Fascin-K41 acetylation/deacetylation regulates tumor metastasis in esophageal squamous cell carcinoma. (PubMed, J Pathol) - "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."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • Fascin • FSCN1 • KAT8 • SIRT7

NP-G2-044 as Monotherapy and Combination Therapy in Patients With Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Novita Pharmaceuticals, Inc.

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Vaginal Cancer • EGFR

Targeting FSCN1 with an oral small-molecule inhibitor for treating ocular neovascularization. (PubMed, J Transl Med) - "Collectively, FSCN1 inhibition could serve as a promising therapeutic approach to block ocular neovascularization."

Journal • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Fascin

NP-G2-044 as Monotherapy and Combination Therapy in Patients With Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Novita Pharmaceuticals, Inc. | Trial completion date: Sep 2023 ➔ Jun 2024 | Trial primary completion date: Mar 2023 ➔ Jun 2024

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Vaginal Cancer • EGFR

EFFECTS OF ANTIFASCIN COMPOUNDS AGAINST LYMPHOMA CELLS IN VITRO (EHA 2023) - "Three antifascin compounds (imipramine, monastrol and NP-G2-044) were tested against three lymphoma cell lines: L-428, HD-LM-2 (positive expression of fascin, Hodgkin lymphoma cell line models) and U937 (negative expression of fascin, histiocytic lymphoma cell line model). Fascin expression was detected in several types of lymphoma including Hodgkin, lymphoblastic, NK, MALT, mantle, and marginal zone lymphoma. Among evaluated compounds, imipramine appears to be the most promising inhibitor of proliferation and migration in fascin-overexpressing lymphoma cells. As might be expected, imipramine is less effective against cells without fascin."

Preclinical • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • FAS • Fascin

Role of fascin in docetaxel resistance acquisition in breast cancer cell models (EACR 2023) - "In proliferation assays, imipramine reduced the viability of resistant MDA-MB-231 cell line in comparison to MDA-MB-231 wild type (IC50 of imipramine: 9.2±4.9 vs 21±1.2µM, p<0.05; IC50 of NP-G2-044: 5.2±1 vs 14.2±2.1µM, p<0.05). Imipramine reduced the viability and migration abilities of the docetaxel-resistant versus wild-type MDA-MB-231 cell line. This study could be a foundation for a better understanding of docetaxel resistance in TNBC and suggests that the repurposed drug imipramine could be contributing to the reversion of this phenotype."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Fascin

The Role of Fascin-1 in Human Urologic Cancers: A Promising Biomarker or Therapeutic Target? (PubMed, Technol Cancer Res Treat) - "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."

Biomarker • Journal • Review • Bladder Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Urology • Urothelial Cancer • FAS • Fascin • MAPK8

Fascin-1 as a druggable target in agressive hepatoblastoma (LCS 2023) - "We explore the effect of Fascin-1 actin-binding activity impairment by using inhibitors NPG2044 and BDP13176, on invasion and migration using Trans-well and wound-healing assays... Fascin-1 is an interesting target in hepatoblastoma, commercialized phase-2 drugs are available and this study will confirm the potential use of those drugs in HB treatment and elucidate by which mechanism Fascin-1 inhibition impacts tumors."

Gastrointestinal Cancer • Hepatoblastoma • Liver Cancer • Oncology • Solid Tumor • Fascin • ITK

NP-G2-044, a First-in-Class Fascin Inhibitor, Inhibits Growth and Metastasis of Gynecologic Cancers (AACR-NCI-EORTC 2022) - "Fascin represents a novel target for cancer therapy. NP-G2-044 acts simultaneously on tumor cells to block tumor metastasis and on intra-tumoral dendritic cells to reinvigorate anti-tumor immune response. These dual mechanisms of action may be ideally suited for long-term and well-tolerated maintenance therapy."

Breast Cancer • Gynecologic Cancers • Oncology • Triple Negative Breast Cancer • EGFR • Fascin

NP-G2-044 as Monotherapy and Combination Therapy in Patients With Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2; N=100; Recruiting; Sponsor: Novita Pharmaceuticals, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Monotherapy • Oncology • Solid Tumor • MRI

Inhibitors of the Actin-Bundling Protein Fascin-1 Developed for Tumor Therapy Attenuate the T-Cell Stimulatory Properties of Dendritic Cells. (PubMed, Cancers (Basel)) - "Systemic administration of Fscn1 inhibitors for tumor therapy may also modulate DC-induced antitumor immune responses."

Journal • Immune Modulation • Inflammation • Oncology • Fascin

Novita Pharmaceuticals Doses First Patient in Phase 1B-2A Clinical Study of NP-G2-044 in Patients with Advanced or Metastatic Solid Tumor Malignancies (PRWeb) - "Novita Pharmaceuticals, Inc...announced that the first patient has been dosed with its first-in-class fascin-inhibitor NP-G2-044 in a Phase 2A clinical trial. The primary objectives of the open-label study in patients with advanced or metastatic solid tumor malignancies is to define the recommended phase 2 doses (RP2Ds) of NP-G2-044 monotherapy and when given in combination with anti-PD-(L)1 therapy and to evaluate the safety, tolerability, and preliminary anti-tumor efficacy of NP-G2-044. Approximately 100 patients are anticipated to be enrolled in this study at multiple cancer centers across the United States. Pharmacokinetic and pharmacodynamic data will also be evaluated from the study."

Trial status • Oncology • Solid Tumor