FDA Orphan Drug Designation Given to NP-G2-044 in Pancreatic Cancer

NP-G2-044 (Prilukae), a novel oral fascin inhibitor, has earned orphan drug designation (ODD) from the FDA for the treatment of pancreatic cancer.¹ This designation covers the use of the agent as monotherapy and in combination with anti–PD-1 immune checkpoint inhibitors (ICIs).

Pancreatic cancer, which affects over 100,000 patients in the United States,² remains highly lethal, with patients often facing treatment resistance and limited options in the advanced disease setting. ODD status supports the endeavor of developing novel treatments for such rare and challenging conditions by providing sponsors with various incentives including tax credits for clinical trials, user fee exemptions, and a potential 7 years of market exclusivity upon approval.³

"FDA [ODD] for our fascin inhibitor represents an important regulatory milestone…and validates [our] scientific and clinical approach in the fight against pancreatic cancer, as it remains one of the most lethal solid tumors with limited therapeutic progress over decades," said Stewart Campbell, CEO of Novita Pharmaceuticals, in a news release.¹ "Fascin inhibition offers a novel approach with the potential to enhance antitumor immune activity and improve outcomes for patients with this devastating disease, and we look forward to continuing advancement of NP-G2-044 to address the high unmet need."

About NP-G2-044

NP-G2-044 is a small molecule inhibitor designed to block tumor metastasis and enhanced immune response.⁴ The agent targets fascin, the primary actin-bundling protein that plays a critical role in tumor cell migration and metastasis. By inhibiting fascin, the drug blocks the motility and invasion of tumor cells and simultaneously activates intratumoral dendritic cells, ultimately leading to the proliferation of CD8-positive T cells.

Preclinical evidence has demonstrated synergistic activity between NP-G2-044 and anti–PD-1 therapy, which enabled the conversion of nonresponsive tumors into responsive tumors. These findings served as the rationale for investigating NP-G2-044 as combination therapy in addition to monotherapy.

Clinical Development and Early Data

NP-G2-044 is under evaluation as monotherapy and in combination with anti–PD-1 therapy in the phase 1/2 NP-G2-044-P2-01 trial (NCT05023486). This trial is a multicenter, open-label study evaluating safety, tolerability, pharmacokinetics and pharmacodynamics, and preliminary antitumor activity of the regimens in patients with advanced or metastatic solid tumors, including those with documented primary or acquired resistance to anti–PD-(L)1 therapy.⁵

Malignancies represented in the patient cohort alongside pancreatic ductal adenocarcinoma (PDAC) include gynecologic cancers (ovarian, endometrial/uterine, fallopian tube, cervical, vulvar, and vaginal), triple-negative breast cancer, esophageal squamous cell carcinoma, cholangiocarcinoma, gastroesophageal junction adenocarcinoma, oropharyngeal squamous cell carcinoma, non–small cell lung cancer, and non–muscle invasive bladder cancer.

In the monotherapy arm, patients are receiving continuously dosed capsules or tablets of NP-G2-044. In the combination arm, NP-G2-044 is administered at 1600 mg or 2100 mg once daily along with previously initiated standard-of-care anti–PD-1 therapy.

Data from the trial, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, showed durable responses among 33 efficacy-evaluable patients receiving combination therapy, with an objective response rate (ORR) of 21% (95% CI, 9%–38.9%).⁴ This ORR included 4 complete responses, 2 of which were in patients with PDAC and gastroesophageal junction adenocarcinoma. The combination’s safety profile was primarily characterized by diarrhea, fatigue, nausea, and transaminitis, which were transient and reversible. These promising efficacy data indicated the therapy’s potential to overcome ICI resistance in PDAC and across multiple tumor types.

The study is ongoing and recruiting a total of approximately 140 adult patients across 18 locations in the United States.

Next Steps in Development

The sponsor has indicated plans for more in-depth biomarker analyses to explore predictors of response and resistance, which will help guide personalized treatment strategies.⁶ In addition, further development of NP-G2-044 in gynecologic cancers has recently advanced into the pivotal phase 3 ULTIMUS-1 trial (NCT07109414), which is enrolling patients with platinum-resistant ovarian cancer.

REFERENCES

1. Novita Pharmaceuticals announces FDA orphan drug designation granted to NP-G2-044 for the treatment of pancreatic cancer. News release. Novita Pharmaceuticals. January 12, 2026. Accessed January 12, 2026. https://tinyurl.com/4mvv93f5

2. Cancer stat facts: pancreatic cancer. US National Institutes of Health. Published 2018. Accessed January 12, 2026. https://tinyurl.com/jhhhzh55

3. Designating an orphan product: drugs and biological products. US Food & Drug Administration. Updated August 12, 2024. Accessed January 12, 2026. https://tinyurl.com/5n77pu2w

4. Kasi A, Birrer MJ, Brown JR, et al. Durable responses in ICI-refractory or acquired resistance: Phase 2 study of NP-G2-044 combined with anti-PD-1 therapy. J Clin Oncol. 2025;43(16_suppl):2513-2513. doi:10.1200/jco.2025.43.16_suppl.2513

5. NP-G2-044 as monotherapy and combination therapy in patients with advanced or metastatic solid tumor malignancies. ClincialTrials.gov. Updated December 5, 2025. Accessed January 12, 2026. https://clinicaltrials.gov/study/NCT05023486

6. 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. News release. Novita Pharmaceuticals. February 25, 2025. Accessed January 12, 2026. https://tinyurl.com/5789m2e8