The global medical community marks World Inflammatory Bowel Disease Day on May 19th each year, focusing on patients suffering from inflammatory bowel disease (IBD).
As many as 10 million IBD patients face ongoing abdominal pain, malnutrition, and bloody stools as part of an ongoing cycle of intestinal obstruction, chronic diarrhoea, and cancer progression.
Clinical evidence highlights that untreated IBD patients face a 70% risk of requiring intestinal resection within 10 years, with early therapeutic intervention facilitating mucosal healing in 75% of cases.
Precision-targeted therapies are emerging as breakthrough strategies as the medical community works to provide relief from the challenges of immune system dysregulation.
Factors influencing the development of IBD
ACROBiosystems offers a comprehensive product portfolio of IBD research solutions, including stable cell lines, highly active recombinant proteins, and inhibitor screening kits.
The company’s solutions span the complete drug development continuum, including target discovery and validation, candidate drug screening and development, and CMC manufacturing and quality control.
ACROBiosystems’ IBD research offering has been designed to accelerate the efficient translation of IBD innovative therapies, rapidly advancing these from foundational research to clinical implementation.
IBD: The ‘immune storm’ within the gut
IBD encompasses a range of chronic inflammatory bowel disorders driven by immune dysregulation, including ulcerative colitis (UC) and Crohn’s disease (CD).
IBD’s pathogenesis is complex, with genetic predisposition converging with environmental triggers (for example, infections and dietary patterns) to disrupt intestinal barrier integrity.
This disruption manifests as epithelial tight junction disruption, permitting luminal antigen leakage into the submucosa via gut microbiota dysbiosis and compromised mucus layer thickness. These breaches initiate hyperactivation of the innate immune system, triggering a self-perpetuating inflammatory cascade.
Activation of the innate immune system is followed by the aberrant release of pro-inflammatory cytokines such as TNF-α and IL-23 by macrophages and neutrophils, which recruit additional immune cells to trigger the ‘initial inflammatory surge.’
The adaptive immune system becomes dysregulated, characterized by impaired regulatory T cell function and hyperactivation of Th1/Th17 cells, subsequently leading to chronic inflammatory cycling and autoantibody production.
The equilibrium between pro-inflammatory cytokines (such as TNF-α, IL-6) and anti-inflammatory mediators (such as IL-10) collapses at the same time, with this imbalance amplifying the ‘cytokine storm’ via NF-κB and JAK-STAT signaling pathways and leading to indiscriminate inflammation propagation.
This immune hyperactivation degrades tight junction proteins and accelerates intestinal epithelial apoptosis, eventually establishing refractory intestinal ulceration.
Pharma giants’ target-driven approach to IBD treatment
A significant number of leading global pharmaceutical companies have prioritized research into IBD therapeutics. For example, in 2023, clinical pipeline projects in this field were reported to increase by 25% year-over-year.
Target innovation is taking place within a tripartite competitive landscape.
TNF-α inhibitors remain market dominants within the cytokine domain, demonstrated by adalimumab successfully reaching over $20 billion in annual sales. The IL-23 target has also emerged as a focal point, with ustekinumab from Johnson & Johnson reaching more than $10 billion in annual sales.
It is also notable, however, that risankizumab from AbbVie has shown a clinical response rate of 60% at 14 weeks in Phase III trials, representing a direct challenge to ustekinumab's market position.
The JAK-STAT pathway has seen innovation in terms of its safety, AbbVie’s upadacitinib achieving a 26% mucosal healing rate with a 1.2% serious infection incidence. These advances have driven 45% annual growth for JAK1-selective inhibitors.
The TYK2 inhibitor deucravacitinib from Bristol Myers Squibb has shown a 40% remission rate with zero thrombotic events, potentially revolutionizing treatment paradigms.
Takeda’s vedolizumab maintains leadership in the field of gut-specific targets, demonstrating α4β7 integrin inhibition with 45% 5-year sustained remission. The oral MAdCAM-1 inhibitor AJM300 potentially opened up a billion-dollar market, and successfully achieved a 63% Phase II response rate.
Emerging target TL1A has arisen as a key contender, with TEV-48574 from Merck demonstrating superior Phase II results of 62% clinical remission and 42% fibrosis reversal. These findings have prompted intensified investments from companies such as Pfizer and Roche, with the TL1A inhibitor market currently anticipated to exceed $5 billion by the year 2030.
The future of IBD therapeutics: Transitioning from monotherapy to multidimensional therapeutic integration
Advances in the characterization of IBD pathogenesis underpin systemic innovation in therapeutic paradigms. This work's core is a multidimensional coordinated framework designed to integrate dual defense mechanisms via a targeted synergy between biologics (for example, azathioprine combined with anti-TNF-α/integrin agents) and immunomodulators.
This framework implements activity-adapted dynamic treatment protocols by establishing multi-pathway inhibitory networks via small-molecule agents (S1P modulators/JAK inhibitors).
Precision medicine implementation utilizes microbiota-targeted modulation (fecal microbiota transplantation/probiotic combinations), genotype-guided interventions (for example, IL-17A/TNF-α dual blockade for NOD2-mutated IBD), and biomarker-stratified therapeutic algorithms.
Innovative modalities feature tissue-selective agents (α4β7 integrin inhibitors/oral MAdCAM-1 antagonists), bifunctional biologics (ustekinumab targeting IL-12/IL-23), and emerging targets such as TL1A inhibitors.
Intestinal organoids and organs-on-chips accelerate target validation and drug discovery by enabling the ground-breaking three-dimensional simulation of the ‘epithelial-immune-microbiota’ interaction system. These developments position IBD therapy at the forefront of a new era of research heralded by multi-omics-guided dynamic precision medicine.
ACROBiosystems pioneers IBD therapeutics via novel solutions
The powerful combination of the accelerated clinical translation of targeted biologics and breakthroughs in AI-driven personalized therapeutics and microbiome-based therapies drives IBD therapeutics toward a paradigm shift, evolving from symptom management to disease-modifying reversal.
ACROBiosystems has developed a wide-ranging product portfolio for IBD research, including stable cell lines, highly active recombinant proteins, and inhibitor screening kits.
The company’s solutions span the entire drug development continuum, including target discovery and validation, candidate drug screening and development, and CMC manufacturing and quality control.
These products are key to accelerating the efficient translation of innovative IBD therapies from foundational research to clinical implementation.
Hot IBD Target Recommendations. Source: ACROBiosystems
| . |
. |
. |
. |
. |
| TNF-alpha |
TL1A |
IL-1 beta |
IL-10 |
IL-10 R alpha |
| IL-17A |
IL-17A & IL-17F |
IL-17E |
IL-17 RA |
IL-17 RA & IL-17 RC |
| IL-22 |
IL-6 |
PD-1 |
PD-L1 |
CTLA-4 |
| ICOS |
Integrin alpha 4 beta 7 |
Integrin alpha E beta 7 |
MAdCAM-1 |
CXCR3 |
| STAT3 |
CD47 |
JAK1 |
TYK2 |
IL23A & IL12B |
| FGF R2 (IIIb) |
FGF R2 (IIIc) |
IL-2 R alpha |
IL-12B |
CD40 |
Intestinal organoids
A range of ready-to-use intestinal organoids and differentiation kits is available to support pioneering IBD research.
Intestinal organoids’ cell composition and arrangement closely resemble the structure of intestinal epithelium, meaning that crypt characteristics are maintained even after prolonged culture.
Their short culture cycle allows the easy freezing and passage of intestinal organoids, while the apical membrane, positioned on the outer layer, represents an optimal interface for absorption testing.
References and further reading
- Ekstedt, N., Jamioł-Milc, D. and Pieczyńska, J. (2024). Importance of Gut Microbiota in Patients with Inflammatory Bowel Disease. Nutrients, 16(13), p.2092. https://doi.org/10.3390/nu16132092.
- Dunleavy, K.A., Raffals, L.E. and Camilleri, M. (2023). Intestinal Barrier Dysfunction in Inflammatory Bowel Disease: Underpinning Pathogenesis and Therapeutics. Digestive Diseases and Sciences, 68(12), pp.4306–4320. https://doi.org/10.1007/s10620-023-08122-w.
- Lu, Q., et al. (2022). Immunology of Inflammatory Bowel Disease: Molecular Mechanisms and Therapeutics. Journal of Inflammation Research, (online) 15, pp.1825–1844. https://doi.org/10.2147/JIR.S353038.
- Tian, C., et al. (2023). Stem cell-derived intestinal organoids: a novel modality for IBD. Cell Death Discovery, (online) 9(1), pp.1–16. https://doi.org/10.1038/s41420-023-01556-1.
Acknowledgments
Produced from materials originally authored by ACROBiosystems.
About ACROBiosystems
ACROBiosystems is a cornerstone enterprise of the pharmaceutical and biotechnology industries. Their mission is to help overcome challenges with innovative tools and solutions from discovery to the clinic. They supply life science tools designed to be used in discovery research and scalable to the clinical phase and beyond. By consistently adapting to new regulatory challenges and guidelines, ACROBiosystems delivers solutions, whether it comes through recombinant proteins, antibodies, assay kits, GMP-grade reagents, or custom services. ACROBiosystems empower scientists and engineers dedicated towards innovation to simplify and accelerate the development of new, better, and more affordable medicine.
Sponsored Content Policy: News-Medical.net publishes articles and related content that may be derived from sources where we have existing commercial relationships, provided such content adds value to the core editorial ethos of News-Medical.Net which is to educate and inform site visitors interested in medical research, science, medical devices and treatments.