Harvest Moon Pharmaceuticals · TNF · Recombinant Proteins
etanercept is a recombinant proteins developed by Harvest Moon Pharmaceuticals. It is approved for therapeutic indications via injectable (others) or intraarticular injection or intravenous (iv) or subcutaneous injection.
| Company | Harvest Moon Pharmaceuticals |
| Drug Class | Recombinant Proteins |
| Molecular Target | TNF |
| Route | Injectable (Others), Intraarticular Injection, Intravenous (IV), Subcutaneous Injection |
| Status | Approved |
etanercept acts on 1 molecular target:
| TNF | tumor necrosis factor (TNFA, TNF-alpha) |
etanercept is developed for 5 unique indications across 2 therapeutic areas.
| Therapeutic Area | Condition | Phase |
|---|---|---|
| Musculoskeletal and connective tissue disorders | Rheumatoid arthritis | ✓ Approved |
| Musculoskeletal and connective tissue disorders | Ankylosing spondylitis | Preclinical |
| Skin and subcutaneous tissue disorders | Psoriasis | Preclinical |
| Musculoskeletal and connective tissue disorders | Psoriatic arthropathy | Preclinical |
| Musculoskeletal and connective tissue disorders | Juvenile idiopathic arthritis | Preclinical |
Sunny Maria M, George Justin J, Mruthyunjaya Prakashini P, Ahmed Sakir S et al.
Goh Su Li SL, Nagra Deepak D, Jayasinghe Madusha M MM, Hassan Rofaida R et al.
Gao Sai S, Yin Ruili R, Shi Jingxuan J, Miao Zhuang Z et al.
Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by keratinocyte hyperproliferation and cytokine-driven immune activation, in which TNF-α plays a central pathogenic role. We developed a layered hydrated silk fibroin (SF) microneedle system (ETA@Hyd MN) with SF tips loaded with etanercept (ETA, a TNF-α inhibitor for psoriasis), for local cutaneous delivery to reduce systemic exposure and rapidly dissolving polyvinyl alcohol (PVA) bases that facilitate retention of the SF tips within the skin. Hydration markedly slowed ETA release, with approximately 80% released at 48 h compared with approximately 75% released within 1 h from microneedles without hydration. In HaCaT cell scratch assays, release media from ETA@Hyd MN attenuated the accelerated wound closure response, resulting in a greater remaining scratch width than that in the model group at 48 h. In an IMQ-induced psoriasis-like mouse model, ETA@Hyd MN improved clinical symptoms, reduced PASI scores, alleviated spleen enlargement, and suppressed epidermal hyperplasia and TNF-α/IL-6 expression. These results demonstrate that ETA@Hyd MN enables sustained ETA release and effectively suppresses inflammation, highlighting its potential for treating inflammatory skin diseases.
Kim Tae-Ho TH, Kim Hyun-Seung HS, You Jungmok J, Kim Yeon-Gu YG
Sialylation is a critical quality attribute of therapeutic glycoproteins, yet strategies to specifically modulate O-glycan sialylation remain underdeveloped compared to N-glycosylation. While N-acetylmannosamine (ManNAc) is widely utilized as an established enhancer of N-glycan sialylation, its efficacy in modulating O-glycan structures has remained largely unexplored across different mammalian hosts. In this study, we investigated ManNAc supplementation as a practical approach for modulating O-glycan sialylation in recombinant Chinese hamster ovary (CHO) cells. Using etanercept and erythropoietin-Fc-fusion protein as models, we found that ManNAc supplementation resulted in a statistically significant, although modest, increase in the proportion of di-sialylated O-glycoforms and the overall content of O-linked sialic acid without compromising cell growth or protein productivity. This enhancement was accompanied by a substantial expansion of the intracellular CMP-sialic acid (CMP-SA) pool. Interestingly, despite increased CMP-SA levels following ManNAc supplementation in human embryonic kidney 293 (HEK293) cells, O-glycan sialylation remained largely unchanged, indicating that responsiveness to ManNAc supplementation differs among cell lines. Our results suggest that ManNAc supplementation can serve as a useful tool for adjusting O-glycan sialylation in CHO cell-based production systems, providing process-relevant insights for biosimilar quality control. Overall, this study provides fundamental mechanistic insights into the use of metabolic precursors to modify the sialylation profiles of O-glycosylated therapeutic glycoproteins.
Baldini Sara S, Schifano Nicolo' N, Fernando Kiyara K, Coschignano Matteo M et al.
Retroperitoneal fibrosis (RPF) is a rare fibroinflammatory disorder characterized by the development of fibrotic tissue around the abdominal aorta, often leading to ureteral entrapment and renal dysfunction. Several pharmacological agents have been implicated as potential triggers. Despite scattered case reports and limited series, comprehensive quantitative assessments of drug-related RPF signals remain scarce. This study aimed to identify and quantify signals of disproportionate reporting of RPF associated with specific medications using data from a large pharmacovigilance database. The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) was queried from 1969 to 2025 to identify RPF-related adverse event reports. Drugs associated with more than twenty RPF reports were included in a disproportionality analysis; this threshold was arbitrarily defined to focus on medications with a relatively higher volume of reports. This selection aimed to ensure adequate statistical power and reduce noise from underreported associations. For each, the Reporting Odds Ratio (ROR), 95% Confidence Intervals (CI), Proportional Reporting Ratio (PRR), chi-square values, and p-values were calculated. A signal was considered statistically significant when PRR > 2, chi-square > 4, and p < 0.05. The total number of reports in the FAERS database was 30,668,520. A total of 1,013 RPF cases were identified. Of these, 392 (38.7%) were linked to eleven drugs, each associated with more than twenty RPF reports. Methysergide showed the strongest association (ROR: 5332.28; 95% CI: 4292.96-6623.21; PRR: 4604.65; chi-square: 429,546.30; p < 0.0001), followed by pergolide (ROR: 923.85; 95% CI: 686.60-1243.09; PRR: 897.76; chi-square: 40,148.64; p < 0.0001) and bromocriptine (ROR: 311.30; 95% CI: 224.78-431.13; PRR: 308.26; chi-square: 11,201.91; p < 0.0001). Several widely used medications such as bisoprolol, atenolol, and metformin also showed significant, though less pronounced, associations (p < 0.0001). The remaining drugs included etanercept, prednisone, rituximab, propranolol, and cyclophosphamide, all of which exhibited significant levels of disproportionate reporting (p < 0.0001). This pharmacovigilance analysis identified multiple medications, spanning different therapeutic classes, that demonstrated a disproportionate association with reports of RPF. Notably, some drugs with well-established safety profiles also emerged as potential signals, warranting increased clinical awareness. While this analysis reveals pharmacovigilance signals suggestive of drug-induced RPF, the observational nature of FAERS data limits causal inference. These findings underscore the need for further clinical research and mechanistic studies to better understand the etiopathogenic role of these agents in RPF development.
Gao Pingping P, Sun Na N, Yang Ning N, Zhao Tingting T et al.
Triple-negative breast cancer (TNBC) remains therapeutically challenging due to its aggressive metastatic potential, high recurrence rates, and lack of effective targeted therapies. Herein, we identified that SOX30 is significantly upregulated in TNBC and correlates with poor clinical prognosis. Functionally, SOX30 specifically drives TNBC metastasis and activates the TNFR2-mediated downstream NF-κB signaling cascade. Mass cytometry profiling of the tumor immune microenvironment revealed that SOX30 facilitates the recruitment of tumor-associated macrophages (TAMs) within pulmonary metastases, a finding corroborated by flow cytometric quantification. Mechanistically, downstream pathway analyses identified that SOX30 induces activation of the TNFR2-NF-κB axis and concurrently upregulates expression of the chemokine CCL20. Therapeutic intervention with CCL20 neutralizing antibodies or small-molecule CCR6 inhibitors effectively attenuated metastatic progression and abrogated TAM infiltration. Strikingly, combinatorial blockade using the TNFR2 inhibitor etanercept together with a CCR6 inhibitor exhibited superior anti-metastatic efficacy relative to control treatments. Collectively, our findings delineate a novel oncogenic SOX30-TNFR2-NF-κB-CCL20/CCR6 axis driving TNBC metastasis. These results establish SOX30 as a promising prognostic biomarker and a potential therapeutic target for anti-metastatic strategies in TNBC.
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