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 | "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

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 | Trial completion date: Aug 2026 ➔ Dec 2027 | Trial primary completion date: Aug 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor

FSCN1 promotes rheumatoid arthritis progression via inhibiting TRIM38-mediated ubiquitination of IGF2BP1 in fibroblast-like synoviocytes. (PubMed, Arthritis Rheumatol) - "Pharmacological inhibition of FSCN1 restrains synovial inflammation and joint destruction by suppressing the aggressive phenotype change of FLS, representing a promising therapeutic strategy against RA."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Osteoarthritis • Pain • Rheumatoid Arthritis • Rheumatology • Targeted Protein Degradation • Fascin • FSCN1 • IGF2BP1 • TRIM38

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

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

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

Z1362873773 (Z773) and NP-G2-044 differentially modulate breast cancer cell migration despite distinct cytotoxic profiles (EACR 2026) - "NP-G2-044 showed lower IC50 values than z773 in both breast cancer lines; however, z773 produced stronger migration inhibition in MDA-MB-231 at 15–20 µM and required higher doses to impact MCF7 migration. These findings support the need for follow-up in vivo evaluation."

Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Fascin • FSCN1

FASCIN AS A NOVEL POTENTIAL PROGNOSTIC BIOMARKER AND THERAPEUTIC TARGET IN T-CELL LYMPHOMA (EHA 2026) - "Cell viability was evaluated using an XTT assay following treatment with anti-fascin compounds (imipramine, a repurposed antidepressant, and NP-G2-044). These findings support further validation and preclinical development of fascin-targeted strategies in TCL. This work was supported by a grant from the FEHH-SEHH and by Ministerio de Ciencia e Innovation through the grant Ramón (Grant RYC2022-037702-I, funded by MCIU/AEI/10.13039/501100011033 and by the ESF+)."

Biomarker • Hematological Malignancies • Lymphoma • Natural Killer/T-cell Lymphoma • Solid Tumor • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • ALK • Fascin • FSCN1

Activity of NP-G2-044 (fascin inhibitor) + anti–PD-1 in ICI-resistant advanced/metastatic solid tumors with expansion in cutaneous squamous cell carcinoma (CSCC). (ASCO 2026) - P1/2 | "NP-G2-044 plus anti–PD-1 demonstrated pan-tumor activity in ICI-resistant advanced/metastatic solid tumors with durable benefit, including responses persisting after treatment cessation. In advanced/metastatic ICI-resistant CSCC, the regimen achieved 50% ORR and 100% disease control with durable CRs. These data support fascin inhibition as a novel DC-activating immunotherapy backbone for immune-resistant CSCC."

IO biomarker • Metastases • Gastroesophageal Junction Adenocarcinoma • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • CD8 • Fascin • IFNG • IL12A

Dual regulation of metabolism and immune contact by a self-reinforcing hydrogel enhances CAR-T-mediated residual tumor clearance and surveillance. (PubMed, J Control Release) - "Specifically, the c-Myc inhibitor JQ1 and bovine serum albumin (BSA)-decorated nanoparticles loaded with the actin cytoskeleton inhibitor NP-G2-044 (BPG) were encapsulated into a reactive oxygen species (ROS)-sensitive hydrogel (JQ1 + BPG@gel). This hydrogel system improved the anti-recurrence efficacy of CAR-T therapy by 9-fold compared with monotherapy while establishing durable immune surveillance via memory T-cell differentiation within lymphoid organs. This research offers an innovative strategy to improve postoperative tumor cure rates and potentiate CAR-T immunotherapy."

Journal • Oncology • CXCL10 • MYC

NP-G2-044 as Monotherapy and Combination Therapy in Patients With Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2 | N=121 | Active, not recruiting | Sponsor: Novita Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2026 ➔ Jun 2026 | Trial primary completion date: Mar 2026 ➔ Jun 2026

Enrollment closed • Monotherapy • Platinum resistant • 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

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

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

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