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Lilly’s Morphic deal is an oral bet in a familiar, crowded α4β7 class
Eli Lilly’s $3.2 billion deal for Morphic, agreed in July 2024, is a bet on a pill, not on a new target. Takeda’s Entyvio (vedolizumab) already blocks integrin α4β7, and the November 2025 chart from Sleuth and Vibe Bio counts 72 α4β7 assets across more than 50 companies, 51 of them active and 21 inactive or of unknown status. Morphic’s MORF-057 is an oral small-molecule α4β7 inhibitor for inflammatory bowel disease (IBD), one of the most competitive areas in immunology and inflammation (I&I).
The interest comes from pairing gut-selective biology and a familiar class with a pill, which could move α4β7 therapy earlier in treatment for patients reluctant to take an infusion or injection.
The active pipeline is early, and Phase 3 is all Entyvio biosimilars
Of the 51 active assets on the November 2025 chart, 25 are preclinical, 4 are in Phase 1, 9 in Phase 2, 8 in Phase 3 and 5 marketed. All eight active Phase 3 entries are vedolizumab biosimilars. The marketed group is vedolizumab, in intravenous and subcutaneous forms, plus three drugs aimed at the closely related α4 subunit (CD49d): natalizumab, a natalizumab biosimilar and carotegrast methyl. Active Phase 2 entries include MORF-057, AbbVie’s ABBV-382, Spyre’s SPY001 and Gilead’s GS-1427.
Active assets split mainly between small molecules (41%) and monoclonal antibodies (36%), and most target I&I, especially IBD. The inactive list shows how hard the class has been: Roche’s etrolizumab is marked inactive after reaching Phase 3, and Phase 2 programs such as firategrast, PN-943 and PTG-100 are marked inactive or unknown.
Late-stage activity is almost entirely biosimilar, so the new value in α4β7 lies in delivery and positioning, not in the target.
Entyvio biosimilars set the bar an oral drug has to clear
After the snapshot, the FDA accepted Alvotech’s AVT16 biosimilar application, with a decision expected in the first quarter of 2027, and Polpharma Biologics told Takeda it expects approval of its PB016 in May 2027. In August 2026, Takeda sued Polpharma under the BPCIA over vedolizumab dosing patents, so US launch timing will depend on the litigation.
Against other advanced orals such as JAK inhibitors and S1P modulators, Sleuth’s view is that a gut-selective α4β7 pill has a stronger safety story. That matters because oral convenience sells only with an acceptable chronic-use safety profile, a lesson traced in Sleuth’s map of pharma’s I&I mechanism stack. An oral also keeps combination flexibility over any two-biologic regimen, an edge that grows once cheaper vedolizumab arrives.
MORF-057’s case rests on dual pharmacology and larger trials
Sleuth and Vibe Bio’s analysis makes a pharmacology argument. Chronic vedolizumab treatment upregulates α4β1 as an escape pathway, and the analysis argues that MORF-057’s roughly 41,600-fold selectivity for α4β7 erodes as α4β1 expression rises. That could allow dual α4β7 and α4β1 inhibition in patients who have failed vedolizumab while keeping gut selectivity in biologic-naive patients, a hypothesis later trials will need to test.
In the 35-patient, open-label Phase 2a EMERALD-1 trial in ulcerative colitis, MORF-057 met its primary endpoint, a 6.4-point reduction in the Robarts Histopathology Index, with 25.7% endoscopic improvement at week 12 and no serious treatment-related adverse events. That trails the roughly 40% the analysis cites for Entyvio, but the comparison is across trials, in a small, mixed population.
In March 2026, Lilly started EMERALD-3, a placebo-controlled ulcerative colitis trial of about 1,400 participants with a 52-week remission endpoint. These trials will show whether oral convenience, clean safety and efficacy after vedolizumab failure justify the $3.2 billion bet.
Assets and phases are from the Sleuth and Vibe Bio chart dated November 19, 2025, which is not exhaustive, shows each asset’s highest stage and lists an asset under each company developing it. Biosimilar filings, litigation and MORF-057 trial status are current as of September 2026. This page is a dated snapshot.
Frequently asked questions about the integrin α4β7 landscape
How many integrin α4β7 drugs are in development?
The Sleuth and Vibe Bio chart dated November 19, 2025 shows 72 α4β7 assets across more than 50 companies, 51 of them active. Of the active assets, 25 were preclinical, and all eight in Phase 3 were vedolizumab biosimilars.
What is MORF-057 and why did Lilly buy Morphic?
MORF-057 is an oral small-molecule α4β7 inhibitor for IBD. Lilly agreed to acquire its developer, Morphic, for $3.2 billion in July 2024, betting that a gut-selective pill in a familiar class can move earlier in treatment than infused or injected biologics.
How did MORF-057 perform in Phase 2?
In the 35-patient, open-label Phase 2a EMERALD-1 trial in ulcerative colitis, MORF-057 met its histology primary endpoint and showed 25.7% endoscopic improvement at week 12.
