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

Trial of NP-G2-044 (Prilukae) Combined With PLD for Treatment of Platinum-Resistant Ovarian Cancer (ULTIMUS-1) (clinicaltrials.gov) - P2/3 | N=380 | Active, not recruiting | Sponsor: Novita Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor

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 | "NP-G2-044, in combination with anti-PD-1 therapy, appears to have clinical activity across multiple cancer types, overcoming both primary and acquired ICI resistance while producing durable responses. Ongoing expansion cohorts and biomarker analyses aim to refine patient selection. These findings underscore NP-G2-044's potential to address metastatic disease and improve cancer immunotherapy outcomes, offering a promising therapeutic option for patients with limited alternatives."

IO biomarker • P2 data • Preclinical • Biliary Cancer • Cholangiocarcinoma • Endometrial Cancer • Esophageal Cancer • Fatigue • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • CD8 • Fascin • GZMB

FSCN1 induces subchondral bone sclerosis in osteoarthritis via modulating actin cytoskeleton dynamics and YAP signaling. (PubMed, Arthritis Res Ther) - "This study suggests that FSCN1 is a key factor in the relationship between mechanical stress, actin cytoskeleton dynamic, subchondral bone sclerosis and OA pathology. Targeting FSCN1 represents a promising pharmacological approach for OA therapy."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • Fascin • FSCN1 • SPP1

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. | Trial completion date: Mar 2026 ➔ Sep 2026 | Trial primary completion date: Dec 2025 ➔ Mar 2026

Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Oropharyngeal Cancer • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Vaginal Cancer • EGFR • MSI

Novita Pharmaceuticals Announces FDA Orphan Drug Designation Granted to NP-G2-044 for the Treatment of Pancreatic Cancer (PRNewswire)

Orphan drug • Pancreatic Cancer

Low YTHDC1 Expression Upregulates FSCN1 to Promote Nuclear F-Actin Formation and Facilitate Double-strand DNA Breaks Repair in TMZ-Resistant Glioblastoma. (PubMed, Adv Sci (Weinh)) - "Although temozolomide (TMZ) is a cornerstone of GBM treatment, its efficacy is often compromised by inherent or acquired resistance, underscoring the urgent need to uncover molecular mechanisms, discover new therapeutic targets, and develop innovative treatment strategies. Importantly, combining the FSCN1 inhibitor NP-G2-044, with TMZ therapy resulted in stronger anti-tumor effects both in vitro and in vivo. In conclusion, the study demonstrates that nuclear F-actin formation in GBM promotes DSB repair and reveals that targeting FSCN1 with NP-G2-044 could be a promising strategy for enhancing treatment outcomes and improving the prognosis for GBM patients."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CDC42 • Fascin • FSCN1 • YTHDC1

Trial of NP-G2-044 (Prilukae) Combined With PLD for Treatment of Platinum-Resistant Ovarian Cancer (ULTIMUS-1) (clinicaltrials.gov) - P2/3 | N=380 | Recruiting | Sponsor: Novita Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor

Thymic Stromal Lymphopoietin Promotes Ozone-induced Inflammation in the Airway. (PubMed, Am J Respir Cell Mol Biol) - "Expression of Fscn1 was greater in bone marrow-derived cDC1s stimulated by TSLP, and ozone-exposed BALB/c mice treated with NP-G2-044 showed lower neutrophils in BALF than BALB/c mice treated with placebo. For conclusion, cDC1 derived Fscn1 was a potential target for ozone-induced neutrophilic airway inflammation via TSLP."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • BATF3 • CRLF2 • Fascin • FSCN1 • TSLP

Trial of NP-G2-044 Combined With PLD for Treatment of Platinum-Resistant Ovarian Cancer (clinicaltrials.gov) - P2/3 | N=380 | Not yet recruiting | Sponsor: Novita Pharmaceuticals, Inc.

New P2/3 trial • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor

Clinical Trial of Metastasis Inhibitor NP-G2-044 in Patients With Advanced or Metastatic Treatment-Refractory Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=23 | Completed | Sponsor: Novita Pharmaceuticals, Inc. | Phase classification: P1a ➔ P1

Phase classification • Breast Cancer • Colon Cancer • Colorectal Cancer • Esophageal Cancer • Genito-urinary Cancer • Liver Cancer • Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor

Targeting Fascin as a Therapeutic Approach to Overcome Oxaliplatin Resistance in Colorectal Cancer (EACR 2025) - "Our findings highlight the key role of fascin in oxaliplatin resistance in CRC. Although the anti-fascin compounds NP-G2-044 and imipramine in monotherapy could be viable therapeutic options, higher concentrations would be required to achieve inhibitory effects comparable to oxaliplatin in resistant cells. However, the combination of fascin inhibitors with oxaliplatin exhibited a great ability to reverse drug resistance, showing promising therapeutic potential to overcome chemoresistance."

IO biomarker • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • Fascin • FSCN1

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. | Trial completion date: Sep 2025 ➔ Mar 2026 | Trial primary completion date: Sep 2025 ➔ Dec 2025

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 Ozone-Induced Airway Responses via Conventional Type 1 Dendritic Cells (ATS 2025) - "Treatment with NP-G2-044 was given to evaluate the impact of fascin on ozone-induced airway responses...CONCLUSIONS TSLP is crucial for ozone-induced AHR and neutrophilic airway inflammation via cDC1s. As the mechanism, fascin derived from cDC1 is associated with neutrophilic airway inflammation."

Stroma • Asthma • Inflammation • Respiratory Diseases • BATF3 • CRLF2 • Fascin • FSCN1 • IL33 • TSLP

Novita Highlights Positive Data from Phase 2 Trial of NP-G2-044 in Patients with Advanced and Metastatic Solid Tumors at 2025 ASCO Annual Meeting (PRNewswire) - P1/2 | N=140 | NCT05023486 | Sponsor: Novita Pharmaceuticals, Inc. | "Among the 45 patients treated with NP-G2-044..., all had progressed on prior anti-PD-(L)1 therapies....An ORR of 21% including three patients with Partial Response (PR) and four patients with Complete Responses (CR) including two Pathologic Complete Responses....Long lasting objective responses have been observed across multiple tumor types, with four patients in ongoing treatment, two of which show duration lasting more than 80 weeks in pancreatic cancer and endometrial cancer....Notable outcomes include continued 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, clinical CR in a cutaneous squamous cell carcinoma patient, and PRs in non-small cell lung cancer and cholangiocarcinoma."

P2 data • Cholangiocarcinoma • Endometrial Cancer • Gastroesophageal Junction Adenocarcinoma • Non Small Cell Lung Cancer • Pancreatic Cancer • Squamous Cell Skin Cancer

THERAPEUTIC TARGETING OF PHENOTYPIC PLASTICITY IN METASTATIC, TREATMENT EVASIVE, RECURRENT BRAFV600E-MUTATED COLORECTAL CARCINOMAS. (DDW 2025) - "More importantly, we show that small-molecule inhibitors of fascin1 namely, NP-G2-044 and imipramine, prevent the emergence of phenotypic plasticity and RSCs in the BEACON trial BrafV600E mutated patient tumor samples. Our findings show, for the first time, that fascin1 SMIs in combination with standard-of-care (doublet/triplet) treatment can prevent the emergence of metastatic, recurrent BrafV600E CRCs and improve OS of patients. The outcomes of our study are readily translatable and provide actionable insight toward solving a major unmet clinical need in the treatment of Braf V600E mutated CRCs."

Metastases • Colorectal Cancer • Oncology • Solid Tumor • EGFR

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