Scientific insights: The Integrin α4β7 landscape in IBD
Eli Lilly and Company bought Morphic for $3.2B in July 2024 – here’s the Integrin α4β7 landscape today.
We worked with our friends at Sleuth to assess the risks of MORF-057 and examine the assets in the space.
First, the landscape:
• 51 assets across 54 companies segmented by phase & development status
• Mostly early-stage: 56% of active assets are preclinical
• Largely split between small molecules (41%) and mAbs (36%)
• Vast majority of assets targeting I&I, particularly IBD
IBD (and I&I broadly) are very competitive spaces and this is not a novel target (LOEs for Entyvio are 2027-2030 with multiple biosimilars in late-stage development) – so why the BD interest?
MORF-057 and other next-gen assets offer the potential of a safe, oral drug. With gut-selective biology, this familiar class can credibly move up the treatment paradigm, especially for patients reluctant to take an infusion or injection. When positioned vs. other “advanced orals” such as JAKs, S1P modulators, etc., there’s a more compelling narrative around safety, while retaining the combo flexibility an oral has over any double-biologic regimen, especially after Entyvio goes generic.
Digging specifically into MORF-057:
• Clever dual pharmacology: Chronic VDZ upregulates α4β1 as an escape pathway – MORF-057’s 41,600x selectivity erodes with this increased expression, enabling dual α4β7/α4β1 inhibition in VDZ-failures while maintaining gut-selectivity in bio-naive patients
• Phase 2 showed 25.7% endoscopic improvement vs Entyvio’s ~40%, but that’s in a mixed population with small n – Phase 2b (n=380) will clarify if the oral convenience + clean safety (zero treatment-related SAEs) + post-VDZ efficacy justify Lilly’s $3.2B bet
We were excited to collaborate with Sleuth on this analysis of the Integrin α4β7 landscape.