DDW 2026 Signalled The Next Era Of Competitive Landscape In IBD

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is a chronic immune-mediated gastrointestinal disorder characterized by relapsing intestinal inflammation and progressive tissue damage. While historically viewed primarily as an inflammatory condition, growing evidence suggests IBD also involves fibrotic complications contributing to issues such as strictures, bowel obstruction, and reduced quality of life. Despite significant therapeutic advances across anti-TNF, anti-IL-23, anti-integrin, and JAK-targeted therapies, many patients continue to experience incomplete response, loss of efficacy over time, or progressive disease, highlighting a persistent unmet need for therapies capable of delivering deeper remission, improved durability, and potential disease modification.

At the recent Digestive Disease Week (DDW) 2026 meeting (May 2–5, 2026), the IBD landscape was portrayed as increasingly competitive and diversified, with emerging players and novel mechanisms challenging established standards of care.

Established Anti-IL-23 Leaders Reinforce Long-Term Durability As Competition Intensifies

At the conference, established players, including Eli Lilly, J&J, and AbbVie, placed clear emphasis on long-term data sets to reinforce the durability and safety and to differentiate their anti-IL-23 assets in IBD amid increasing competitive pressure from novel entrants. Updates on anti-IL-23p19 therapies, including Lilly’s Omvoh and AbbVie’s Skyrizi, alongside J&J’s Tremfya, consistently highlighted sustained efficacy, stable safety profiles, and biomarker improvements across broader patient populations, including more complex and higher-risk groups.

The strategic intent behind this messaging is clear. As innovation within the anti-IL-23 class shifts toward improved convenience, through oral agents and extended half-life biologics, established players are reinforcing confidence in long-term disease control to retain market share.

Convenience-Led Innovation Reshapes Competition Within The Anti-IL-23 Class

In light of increasing life cycle management across the anti-IL-23 class, data presented at DDW 2026 positioned J&J’s Icotyde (anti-IL-23R) as a potentially disruptive asset, representing the first targeted oral peptide designed to selectively inhibit the IL-23 receptor in a treatment landscape where biologics are exclusively provided in an injectable format. Unlike established anti-IL-23 monoclonal antibodies, Icotyde offers the advantage of oral administration in a class increasingly focused on convenience and durability, as seen with messaging efforts from established players regarding convenience of subcutaneous administration using push-pens or on body injectors. Notable in this regard, AbbVie’s recent supplementary filing for subcutaneous induction dosing of Skyrizi, expected to be approved in late 2026, underscores continued emphasis on differentiation through patient convenience. However, as oral options such as Icotyde enter the IBD market in 2028+, coupled with lessons from patient experience in dermatology where Icotyde is currently approved in plaque psoriasis, oral therapies could drive a paradigm shift in IBD management.

Alongside oral dosing, presentations at DDW 2026 also highlighted a focus on extending dosing intervals, with next-generation antibodies engineered to improve pharmacokinetics without compromising efficacy. Most notably, Spyre Therapeutics presented early data for SPY003 (YTE-engineered anti-IL-23p19), a monoclonal antibody designed to significantly prolong half-life through enhanced FcRn binding. Results from the Phase 1 trial confirmed a ~threefold half-life extension versus current standards, supporting the potential for quarterly or even bi-annual dosing.

This approach reflects a broader trend toward convenience-led innovation, where improvements in administration and patient burden are becoming as strategically important as efficacy gains. By targeting similar epitopes to established agents like risankizumab while extending exposure, SPY003 is positioned as a direct life cycle challenger, aiming to retain efficacy parity while reducing treatment burden.

Half-life extension is also being applied to next-generation multi-target biologics. Xencor presented preclinical data for XmAb412 (dual anti-IL-23/anti-TL1A inhibitor). By integrating two complementary and key inflammatory pathways into a single long-acting molecule, this approach points toward a future where durability is paired with broader pathway coverage, potentially enhancing efficacy while maintaining infrequent dosing.

While established anti-IL-23 leaders continue to anchor their positioning on long-term efficacy and safety data, therapies with extended half-life formulations introduce a new axis of competition centered on treatment convenience. Reduced dosing frequency has the potential to lessen treatment burden and support long-term adherence, particularly in chronic diseases like IBD where sustained compliance is critical.

Anti-TL1A Therapies Shift The Conversation Beyond Inflammation

At DDW 2026, anti-TL1A developers Merck and Genentech positioned tulisokibart and afimkibart as therapies targeting both the inflammatory and fibrotic components of IBD. This At DDW 2026, anti-TL1A developers Merck and Genentech positioned tulisokibart and afimkibart as therapies targeting both the inflammatory and fibrotic components of IBD. This marks a key shift away from the traditional view of IBD as a purely inflammatory disease toward an immuno-fibrotic paradigm, as reinforced in multiple scientific sessions and satellite symposia. The emphasis on fibrosis reflects a broader unmet need in IBD. While current standards of care effectively target inflammation, fibrotic progression, driving strictures, obstruction, and long-term complications remain largely unaddressed.

TL1A inhibitors are therefore being positioned as a potential step toward disease modification, with the ability to impact disease progression. If validated in ongoing Phase 3 clinical trials, this dual anti-inflammatory and anti-fibrotic profile could represent a meaningful point of differentiation in an otherwise crowded cytokine landscape. However, while anti-fibrotic effects are positioned as a potential differentiator for this class, clinical evidence is yet to be demonstrated and this effect remains limited to evidence generated in preclinical in vitro and ex vivo studies.

Novel Mechanisms Gain Traction As The Oral Treatment Landscape Expands

Beyond incremental innovation within established pathways, data presented at DDW 2026 reinforced growing interest in first-in-class mechanisms, led by Abivax and its lead asset obefazimod (miR-124 upregulator). As an oral small molecule that upregulates microRNA-124, obefazimod represents a fundamentally different approach to immunomodulation, moving upstream of traditional cytokine blockade and positioning itself as a potential disruptor in the IBD landscape.

Notably, at DDW 2026, Abivax placed specific emphasis on at-risk populations, particularly elderly patients, where treatment decisions are often constrained by safety concerns. Data demonstrated comparable efficacy and no new safety signals in elderly patients, helping to de-risk the asset in a population frequently underrepresented in clinical trials. This targeted communication reflects a clear pre-launch strategy to build physician confidence in a novel mechanism ahead of its anticipated UC approval in mid-2027.

Building on the theme of novel mechanisms, presentations at DDW 2026 also reflected renewed interest in next-generation oral immunomodulators beyond JAKs, including mufemilast (PDE4 inhibitor). As a PDE4 inhibitor, mufemilast targets a pathway previously explored in inflammatory diseases but not successfully established in IBD. Early data at DDW 2026 demonstrated encouraging remission rates and sustained efficacy through 24 weeks, including in biologic-experienced patients, alongside a favorable tolerability profile.

Mufemilast's positioning will depend on whether next-generation PDE4 inhibitors can overcome historically modest efficacy and tolerability-driven limitations as the oral treatment landscape continues to expand.

Combination Approaches Aim To Overcome Efficacy Ceilings In Refractory Disease

Despite continued innovation within single mechanisms, presentations at DDW 2026 reinforced a key limitation in IBD management: efficacy plateaus in heavily pretreated patients, driving renewed interest in combination-based approaches.

J&J led this narrative at DDW 2026 with JNJ-78934804 (anti-IL-23/TNF-α dual inhibitor), the first fixed-dose co-antibody simultaneously targeting IL-23 and TNF-α. Across both CD and UC, the asset demonstrated clinically meaningful improvements over established monotherapies, guselkumab and golimumab, particularly in highly refractory populations, while maintaining a safety profile consistent with its individual components. This reinforces the rationale that dual pathway blockade within a single molecule may unlock incremental efficacy without the added complexity of combining separate agents.

Conclusion

Collectively, these developments suggest the future IBD landscape will likely be shaped not only by achieving remission but by how effectively therapies can deliver durable disease control, improve convenience, address structural disease progression, and differentiate within an increasingly competitive treatment environment. To summarize, key points to note from IBD landscape include:

• Long-term durability becomes the new baseline: Established anti-IL-23 therapies increasingly leveraged long-term efficacy and safety data to reinforce physician confidence and defend market positioning as competition intensifies.
• Convenience emerges as a critical differentiator: Oral anti-IL-23R therapy, subcutaneous induction strategies, and extended half-life biologics suggest dosing flexibility and reduced treatment burden will play a growing role in therapy selection.
• Disease modification moves beyond inflammation alone: Anti-TL1A developers positioned anti-fibrotic potential as a key differentiator for the class, reflecting growing focus on structural disease progression.
• Novel oral mechanisms continue to gain momentum: Emerging approaches, such as microRNA modulation and next-generation PDE4 inhibition, highlight expanding interest beyond established cytokine pathways.
• Combination strategies target refractory disease: As efficacy plateaus emerge across established mechanisms, dual-pathway inhibition and combination-based approaches are increasingly being explored.

About The Authors

Gaja Gasiorek, MPhil, is a senior business analyst at Lifescience Dynamics, specializing in immunology with a focus on inflammatory bowel disease . She has over four years of experience in this field, bringing expertise in market research, competitive intelligence, and strategic analysis. Prior to joining Lifescience Dynamics, Gaja worked at a market research firm specializing in competitive intelligence and held various roles in diagnostics-focused startups. She holds a BSc in biotechnology, where she conducted research on gene-editing technologies, including CRISPR-Cas9. Additionally, she earned an MPhil in bioscience enterprise from the University of Cambridge, where she gained in-depth knowledge of drug discovery, development, and the pharmaceutical industry strategic landscape from leading industry experts.

Usman Shabbir, BSc, Ph.D., is a business analyst with experience supporting CI projects across indications including oncology and rare disease therapy areas. With a Ph.D. in chemistry from University College London, Usman developed novel chemical reactions designed to accelerate drug discovery processes in the pharmaceutical industry. Building on this scientific foundation, Usman has created therapy area dashboards that synthesize data from multiple sources to provide stakeholders with an insightful picture of the competitive landscape. This work has led to an in-depth understanding of market dynamics and evolving trends in the therapeutic space.