Inflammatory Bowel Disease (IBD): Emerging Targets and Next Generation of Antibody Solutions

RenSuper Biologics™ Autoimmune Disease Series | Part 2

Inflammatory bowel disease (IBD)—primarily Crohn’s disease (CD) and ulcerative colitis (UC)—is a chronic, relapsing condition and one of the fastest-growing immune-mediated diseases, affecting more than 10 million people worldwide. Despite two decades of biologic therapy, achieving long-term, durable remission remains an ongoing challenge (Hracs, et al. 2025).

Around 40% of patients do not respond initially, 30–50% lose response over time, and others retain persistent inflammation. The field is therefore moving beyond broad inflammatory suppression toward the mechanisms driving disease progression (Kennedy, et al. 2019).

From Broad Immunosuppression to Precision Immunology

IBD treatment is shifting from broad immunosuppression toward precise targeting of the immune networks that drive intestinal inflammation, immune cell trafficking, and tissue remodeling.

Current biologics reflect this progression: TNF-α inhibitors established the first successful approach to neutralizing a key inflammatory driver. α4β7 integrin blockade selectively limits immune cell trafficking into the gut (Feagan, et al. 2013). More recently, IL-23 inhibitors demonstrated the clinical potential of selectively targeting cytokine pathways that sustain chronic intestinal inflammation (D’Haens, et al. 2022; Ferrante, et al. 2022; D’Haens, et al. 2023).

However, despite these advances, key challenges remain:

• Primary non-response and loss of response: Many patients never respond or later lose benefit.
• Incomplete disease control: Deep, durable remission and complete mucosal healing remain difficult.
• Progression beyond inflammation: Persistent immune activation can contribute to complications Persistent immune activation can drive fibrosis and strictures, particularly in Crohn’s disease (Hassan-Zahraee, et al. 2022). 
• Need for improved therapeutic precision: Patient heterogeneity requires targeting distinct mechanisms and complementary inflammatory pathways.

These needs are driving therapies beyond inflammatory suppression. TL1A (TNFSF15), for example, may address both intestinal inflammation and fibrosis (Sands, et al. 2024; Feagan, et al. 2025).

► Current IBD Biologics Landscape:

► Emerging TL1A-Targeting Antibody Landscape:

Biocytogen’s Focus: Accelerating IBD Therapeutic Antibody Discovery

Biocytogen’s RenSuper Workstation™ combines fully human antibody discovery capabilities with a growing portfolio of 100+ autoimmune disease antibody programs, including IBD-relevant programs, to help partners identify and advance therapeutic antibody candidates faster.

Powered by RenMab®, RenLite®, and RenNano®, our portfolio spans mAbs, common-light-chain antibodies (cLC Abs), and heavy-chain-only antibodies (HCAbs) across established and emerging IBD targets—providing ready-to-advance starting points for differentiated IBD biologics.

We highlight three strategically IBD targets shaping the next generation of therapies, each addressing distinct limitations of current treatment paradigms:

1. TL1A (TNFSF15): Expanding Beyond Inflammation

Emerging clinical target with multiple Phase 3 programs in IBD. TL1A plays a role in both intestinal inflammation and fibrosis, offering a differentiated opportunity to address unmet needs beyond inflammatory control—including stricturing disease and incomplete mucosal healing.

• RenMab® mAbs – Superior affinity and functional blocking activity compared with benchmarks.
• RenLite® cLC Abs – Sub-nanomolar affinity and potent blockade, providing a plug-and-play foundation for next-generation bispecific designs. 

2. TNF-α: Reimagining a Proven Target

Established standard-of-care target for IBD. Despite multiple approved therapies, primary non-response, immunogenicity-driven loss of efficacy, and limited tissue penetration continue to impact long-term disease control.

• RenNano® HCAbs – High affinity for human TNF-α and potent blocking activity.
• Differentiation – The ultra-compact HCAb format offers potential for enhanced penetration into inflamed gut tissues and supports exploration of alternative delivery strategies, including localized GI approaches. 

3. IL-23A: Building on Clinical Success

• RenMab® mAbs – Strong binding to both human and cynomolgus monkey IL-23A with functional blocking activity.

Blocking Assay: Lead IL-23A blocking candidates (RM3-RM18) demonstrate IL-23 neutralization activity, providing a foundation for further affinity and functional optimization. 

Bridging the Preclinical Translational Gap with Biocytogen’s IBD Mouse Models

IBD models are difficult to establish reproducibly because outcomes vary with strain, microbiota, housing, induction protocol, and timing. Biocytogen’s experienced in vivo team uses optimized, well-controlled protocols to deliver robust and consistent models.

Our fit-for-purpose strategy combines mechanistically distinct models with clinical, histologic, and pharmacodynamic readouts—helping distinguish general anti-inflammatory activity from target-specific effects and strengthen translational evidence.

Biocytogen’s comprehensive IBD model portfolio:

• Acute and chronic DSS-induced colitis: DSS (dextran sulfate sodium) disrupts the epithelial barrier, allowing luminal antigens to drive innate inflammation and mucosal injury. Acute studies assess rapid colitis and treatment response; repeated cycles evaluate persistent inflammation, tissue remodeling, and fibrosis.
• TNBS-induced colitis: TNBS (trinitrobenzene sulfonate) haptenizes colonic proteins, triggering T-cell–associated inflammation with often-transmural injury and Th1/Th17 features. It complements DSS with a more immune-mediated setting.
• (New) Anti-CD40 antibody–induced colitis: Agonistic CD40 activation drives rapid, innate immune–dominant intestinal inflammation through myeloid-cell activation and inflammatory cytokine signaling, including the IL-12/IL-23 axis. This model provides a mechanistically distinct setting for evaluating therapies targeting innate immune and cytokine pathways.
• Adoptive T-cell transfer colitis: A chronic, adaptive-immune-driven model for immunomodulatory therapies, including anti-TNF and CD4 approaches, that complements chemical injury models.
• Target-humanized models and integrated readouts: Humanized strains enable direct testing against human-specific targets. Studies can combine body weight, disease activity index, colon measurements, H&E histopathology, and optional cytokine, IHC, and Sirius Red analyses to link phenotype, mechanism, and tissue response.

► List of IBD-related targeted humanized mice at Biocytogen:

► Explore Biocytogen’s IBD mouse models and validation datasets. [Link]

Partner With Us: Why Choose Biocytogen?

Biocytogen supports precision IBD drug development from antibody generation through translational validation.

RenMab®, RenLite®, and RenNano® support conventional, bispecific-ready common-light-chain, and heavy-chain-only antibodies. Partners can begin with de novo discovery or existing assets, then evaluate candidates in target-humanized mice and validated DSS, TNBS, or T-cell-transfer, CD-40-induced IBD models using efficacy, histopathology, biomarker, and pharmacodynamic endpoints—all within one integrated workflow.

[Contact us to get started]      [Subscribe to our latest blog on LinkedIn]

Up next in our Autoimmune Disease Series, Part 3: Asthma & Type 2 Inflammation- Antibody Solutions From Upstream Alarmins to Downstream Effectors. Stay tuned!

Frequently Asked Questions: Drug Development for Inflammatory Bowel Disease

1. What biologic therapies are currently available for inflammatory bowel disease (IBD)?

Current IBD biologics primarily target TNF-α, α4β7 integrin, IL-12/23, and IL-23. They reduce inflammation and support induction and maintenance of remission in CD and UC, but primary non-response, loss of response, and incomplete mucosal healing continue to drive next-generation development.

2. Why is TL1A considered a promising therapeutic target for IBD?

TL1A (TNFSF15) contributes to both intestinal inflammation and fibrosis. Promising clinical efficacy and multiple Phase 3 anti-TL1A programs suggest that inhibiting TL1A could address inflammatory activity and tissue remodeling, potentially improving outcomes beyond conventional anti-inflammatory therapy.

3. How do IL-23 inhibitors differ from TNF inhibitors in IBD?

Both target inflammatory pathways, but they regulate different aspects of the immune response. TNF-α inhibitors suppress a central inflammatory cytokine and have anchored biologic therapy for over two decades. IL-23 inhibitors more selectively disrupt a pathway that maintains pathogenic Th17 responses; favorable efficacy and safety making them one of IBD’s fastest-growing biologic classes.

4. Why are different antibody formats important for IBD drug development?

Antibody architecture should match target biology. Conventional mAbs suit many validated targets; cLC Abs facilitate bispecific development; and smaller HCAbs may improve tissue penetration and enable flexible designs, including localized gastrointestinal delivery.

5. Why choose Biocytogen for your IBD biologic discovery?

Biocytogen has developed a portfolio of fully human antibody library targeting multiple clinically relevant IBD pathways using its proprietary RenMab®, RenLite®, and RenNano® discovery platforms. These platforms enable the generation of diverse antibody modalities, supporting the discovery of differentiated therapeutics against both established and emerging IBD targets such as TNF-α, IL-23A, and TL1A.

6. Why choose Biocytogen’s mouse models for preclinical IBD drug development?

Biocytogen pairs established DSS, TNBS, and adoptive T-cell-transfer colitis models with single- and multi-target humanized mice. This enables human-specific antibodies, combinations, and multispecifics to be tested in relevant immunocompetent settings. Integrated antibody discovery and in vivo pharmacology connect candidate generation with efficacy, histopathology, biomarker, and pharmacodynamic analyses for fit-for-purpose target validation, dose selection, and mechanism-of-action assessment.

► Additional Resources:

• Blog: Autoimmune Disease Series, Part 1
• Detailed Autoimmune asset list: Autoimmune Antibody Assets | Biocytogen
• Browse our programs for more: Autoimmune Disease Antibody Programs | Biocytogen
• Explore IBD mouse models and efficacy case studies: IBD Mouse Models | Biocytogen

► References:

1. Hracs L, Windsor JW, Gorospe J, et al. Global evolution of inflammatory bowel disease across epidemiologic stages. Nature. 2025;642(8067):458–466. 
2. Kennedy NA, Heap GA, Green HD, et al. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn’s disease: a prospective, multicentre, cohort study. Lancet Gastroenterol Hepatol. 2019;4(5):341–353. 
3. Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699–710. 
4. D’Haens G, Panaccione R, Baert F, et al. Risankizumab as induction therapy for Crohn’s disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022;399(10340):2015–2030.
5. Ferrante M, Panaccione R, Baert F, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the phase 3 FORTIFY maintenance withdrawal trial. Lancet. 2022;399(10340):2031–2046. 
6. D’Haens G, Dubinsky M, Kobayashi T, et al. Mirikizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2023;388(26):2444–2455. 
7. Hassan-Zahraee M, Ye Z, Xi L, et al. Antitumor necrosis factor-like ligand 1A therapy targets tissue inflammation and fibrosis pathways and reduces gut pathobionts in ulcerative colitis. Inflamm Bowel Dis. 2022;28(3):434–446. 
8. Sands BE, Feagan BG, Peyrin-Biroulet L, et al. Phase 2 trial of anti-TL1A monoclonal antibody tulisokibart for ulcerative colitis. N Engl J Med. 2024;391(12):1119–1129.
9. Feagan BG, Sands BE, Siegel CA, et al. Safety and efficacy of the anti-TL1A monoclonal antibody tulisokibart for Crohn’s disease: a phase 2a induction trial. Lancet Gastroenterol Hepatol. 2025;10(8):715–725.