Targeted Therapies for Inflammatory Bowel Disease (IBD)

Inflammatory Bowel Disease (IBD) is a chronic and relapsing gastrointestinal condition, primarily including Ulcerative Colitis (UC) and Crohn's Disease (CD). UC is confined to the mucosal layer of the colon and presents with continuous inflammation and ulceration, with hallmark symptom being mucus and bloody diarrhea. CD, on the other hand, can affect the entire gastrointestinal tract—especially the terminal ileum and colon—with transmural, segmental lesions that often cause abdominal pain, intestinal strictures, or fistula formation, which significantly impair patients' quality of life (Figure 1).

Figure 1. Classification and Main Clinical Features of Inflammatory Bowel Disease (IBD) [1] (A. Proctitis; B. Left-sided colitis; C. Extensive colitis. Differences between UC and CD)

From 1990 to 2021, the global incidence of IBD has increased by 88.30%, reaching 375,140 cases. It is projected that by 2040, the global IBD patient population will exceed 20 million, making it a newly emerging global public health crisis. Moreover, there is a growing trend of younger individuals being diagnosed with IBD each year [3].

Pathogenesis of IBD

IBD arises from a complex interplay of factors. Genetic mutations increase susceptibility, while immune dysregulation triggers inflammatory attacks on healthy gut tissue. Imbalances in gut microbiota and external factors—like poor diet or infections—can further disrupt intestinal homeostasis.

These overlapping causes lead to wide variability in symptoms, disease course, and treatment response. Most patients need long-term therapy, with frequent relapses—especially in Crohn’s, where recurrence exceeds 60%. With no cure yet, there remains substantial need for improved treatments.

Figure 2. Pathogenic Factors of Inflammatory Bowel Disease (IBD) [4]

Current Landscape of Targeted Therapies for IBD

Conventional IBD treatments (e.g., aminosalicylates, corticosteroids) offer symptom relief but fall short in long-term efficacy and safety. Biologics, with higher selectivity and better outcomes, are reshaping care.

1. Inflammatory Response Control

Key therapeutic targets include:

→ Tumor Necrosis Factor-alpha (TNFα): Rapid Inflammation Control
TNFα and IL-12/IL-23 inhibitors marked major advances in IBD treatment, helping control symptoms and inflammation. While drugs like Adalimumab and Ustekinumab remain common, their effectiveness can be limited by resistance and safety issues. Newer therapies are now targeting alternative inflammatory pathways.

→ IL-12, IL-23, and Their Receptors: Reduction of Chronic Gut Inflammation   

• Ustekinumab: Targets the shared p40 subunit; approved for UC/CD since 2009.
• Guselkumab: Selective IL-23 p19 blocker; approved in 2025 for Crohn’s.
• Other IL-23p19 inhibitors: Include Risankizumab (AbbVie, 2019) and Mirikizumab (Eli Lilly, 2023).

→ Emerging Targets: TL1A and OSMRβ

A TNF-like cytokine that activates DR3 to drive inflammation and fibrosis via Th17 cells, cytokine release, and fibroblast activation. Both forms are active; the soluble form may serve as a biomarker.

Figure 3. Mechanism of Action of TL1A [5]

Targeting TL1A offers a dual approach by reducing both inflammation and fibrosis, positioning it as a potential disease-modifying therapy for IBD. With gaps in current treatment efficacy, TL1A is gaining momentum as a promising, safe option that’s attracting significant interest from global pharmaceutical companies.

Although no TL1A-targeted drugs are approved yet, 2023 marked significant momentum:

• Merck acquired Prometheus Biosciences for $10.8 billion, securing the TL1A antibody Tulisokibart (PRA-023 / MK-7240)—the largest autoimmune M&A to date.
• Sanofi licensed Duvakitug (TEV574) from Teva for $1.5 billion.
• Roche bought Telavant from Roivant for $7.1 billion, obtaining rights to PF-06480605 (now RG-6631 / RVT-3101), originally developed by Pfizer.

Clinical results have highlighted TL1A antibodies as top IBD candidates. In 2024, AbbVie licensed FG-M701 from Mingji Biopharma for $1.7B.

OSMRβ, found in gut stromal cells, drives inflammation and fibrosis via OSM and IL-31 signaling. Vixarelimab, an anti-OSMRβ antibody from Roche and Genentech, is in Phase II trials for ulcerative colitis.

2. Inhibiting Immune Cell Adhesion and Migration

Representative targets: Integrin α4β7, MAdCAM-1

This approach aims to block the interaction between integrins and their ligands on vascular endothelial cells, thereby preventing lymphocytes from crossing the endothelium and migrating to inflamed sites.

• Vedolizumab blocks α4β7 from binding to MAdCAM-1, without affecting α4β1–VCAM-1 interactions—preserving CNS immune surveillance and avoiding PML risk. It’s especially suited for patients unresponsive to conventional or anti-TNFα therapies.
• Ontamalimab (SHP64), a MAdCAM-1 inhibitor from Pfizer later acquired by Takeda, was discontinued due to the absence of a licensing partner.

3. Promoting Tissue Repair

Key target: TGF-β (Transforming Growth Factor Beta)

TGF-β is a multifunctional cytokine that promotes M2 macrophage differentiation, dampens inflammation, and supports tissue repair by inducing ECM synthesis.
A key product in this space is Modulen, a TGF-β2-enriched nutritional formula launched in China in February 2025. With good taste and broad use, it's especially suited for pediatric patients.

Figure 4. Mechanisms of Action of Inflammatory Bowel Disease (IBD) Drugs

The progression of biologic targets in IBD—from early TNFα inhibitors to integrins, interleukins, and now novel targets like TL1A—highlights a strategic shift from symptom control to precision and full immune modulation. Treatment choice depends on disease type, patient tolerance, and individual needs, with combination therapies sometimes required.

Below is a summary of approved and investigational targeted therapies for Ulcerative Colitis (UC) and Crohn’s Disease (CD):

Figure 5. Approved and Investigational Targeted Therapies for Ulcerative Colitis (UC) [6]

Figure 6. Approved and Investigational Targeted Therapies for Crohn’s Disease (CD) [6]

KACTUS Solutions for IBD Research

The growing demand for IBD treatments is driving continuous expansion of the related pharmaceutical market, and each innovative therapy brings new hope to patients. KACTUS offers a wide range of high-quality recombinant proteins essential for IBD drug development. These products cover key targets such as TNFα, IL-23, TL1A, integrins, and more—supporting research needs across all stages of development.

Example Data:

Immobilized Human TNFSF15 Trimer, His Tag at 1 μg/ml (100 μl/Well) on the plate. Dose response curve for Anti-TNFSF15 Antibody, hFc Tag with the EC50 of 3.4 ng/ml determined by ELISA (QC test).

Immobilized Human OSMR beta, His Tag at 1 μg/ml (100 μl/Well) on the plate. Dose response curve for Anti-OSMR Antibody, hFc Tag with the EC50 of 3.7 ng/ml determined by ELISA (QC Test).

Human DR3, hFc Tag captured on CM5 Chip via Protein A can bind Human TNFSF15 Trimer, His Tag with an affinity constant of 0.10 nM as determined in SPR assay (QC test).

Immobilized Human ITGA4&ITGB7, His Tag at 1 μg/ml (100 μl/well) on the plate. Dose response curve for Anti-ITGA4 Antibody, hFc Tag with the EC50 of 5.0 ng/ml determined by ELISA (QC Test).

 

References

[1] Inflammatory Bowel Disease Biomarkers. doi: 10.1002/med.21893.

[2] Global, regional, and national burden of inflammatory bowel disease, 1990–2021: Insights from the global burden of disease 2021. doi: 10.1007/s00384-024-04711-x.

[3] Changing epidemiology of inflammatory bowel disease in children and adolescents. doi: 10.1007/s00384-024-04640-9.

[4] New Insights into the Role of Oral Microbiota Dysbiosis in the Pathogenesis of Inflammatory Bowel Disease. doi: 10.1007/s10620-021-06837-2

[5] TL1A inhibition for inflammatory bowel disease treatment: From inflammation to fibrosis. doi: 10.1016/j.medj.2024.03.010.

[6] Understanding the therapeutic toolkit for inflammatory bowel disease. doi: 10.1038/s41575-024-01035-7

[7] Landscape and predictions of inflammatory bowel disease in China: China will enter the Compounding Prevalence stage around 2030. doi: 10.3389/fpubh.2022.1083211.

[8] Diagnosis and management of inflammatory bowel disease. doi: 10.1111/jebm.12626.

[9] Pathophysiology of Inflammatory Bowel Diseases. doi: 10.1056/NEJMra2002697.

[10] Inflammatory bowel disease: recent developments. doi: 10.1136/archdischild-2023-325668

[11] Review article: Novel therapies in inflammatory bowel disease – An update for clinicians. doi: 10.1111/apt.18294.

[12] Pathophysiology of Inflammatory Bowel Disease: Innate Immune System. doi: 10.3390/ijms24021526.

[13] How Can a Polymeric Formula Induce Remission in Crohn’s Disease Patients? doi: 10.3390/ijms22084025.