Early Morphic data hint at a threat to Entyvio

Hopes rise that Morphic might have cracked the conundrum of oral integrin inhibitors.

Watch out Takeda: Morphic Therapeutic is after your inflammatory bowel disease drug Entyvio. The smaller group reported promising early data today with its lead project, MORF-057, which crucially is given orally versus Entyvio’s intravenous infusion.

Both assets inhibit alpha 4 beta 7 integrin, and Morphic hopes that MORF-057, like Enyvio, will eventually be used in inflammatory bowel disease. The smaller group still has a way to go, but its shares rose 72% this morning on the back of phase I pharmacodynamic data.

Those results, from the single-ascending dose portion of the phase I trial, found that, 12 hours after one dose, healthy volunteers had receptor mean occupancy levels of over 95% with the three highest doses of MORF-057, 100mg, 150mg and 400mg.

During a conference call today Morphic executives described these results as “spectacular”. They had hoped to see at least 90% receptor occupancy for the chosen dose of MORF-057 at steady-state dosing.

“The fact that we’re greater than 95%, and in many subjects we're saturating at those higher doses, suggests we’re having an equivalent type of effect [to Entyvio],” said Bruce Rogers, Morphic's chief scientific officer, although he conceded that no clinical head-to-head trials versus the Takeda project had been carried out.

Staying low

The project was also “as safe as can be”, Morphic’s chief executive, Praveen Tipirneni, said, adding that the group would keep the dose of MORF-057 low in future.

What this means for dose selection in an upcoming phase II study in ulcerative colitis is unclear, as Morphic is playing its cards close to its chest. In any case, the group is still awaiting results from the multiple-ascending dose portion of its phase I trial, plus a food effect study, both due mid-year, before it will decide about the mid-stage trial design.

Mr Tipirneni was clear about Morphic’s target: “We’ve always said that we wanted to be an oral Entyvio.” And no wonder: the sellside expects Takeda’s antibody to bring in $5.5bn at its peak in 2024, according to EvaluatePharma.

This is despite Entyvio’s label containing a warning for progressive multifocal leukoencephalopathy, something Morphic hopes MORF-057 might avoid. PML is linked with inhibition of the alpha 4 beta 1 receptor, and Morphic said it did not see quantifiable levels of alpha 4 beta 1 receptor occupancy in its study.

Morphic now needs data in patients to back up the idea that the project could have a similar performance to Entyvio. Though this will take time, hopes have now been raised for MORF-057 and perhaps Morphic’s entire pipeline, which is exclusively made up of oral integrin inhibitors.

Selected integrin inhibitors for in development for inflammatory bowel disease
Product Company Indication Description Note
Phase III
AJM300 EA Pharma/ Kissei Pharmaceutical Ulcerative colitis  Oral alpha 4 beta 1 integrin & alpha 4 beta 7 integrin inhibitor Jan 2021: primary endpoint hit, companies planning filing in Japan
Etrolizumab Roche Ulcerative colitis, Crohn's Subcutaneous anti-beta 7 integrin MAb Aug 2020: mixed data in UC; Bergamot ph3 in Crohn's to complete Jul 2021
Phase II
PN-10943 Protagonist Therapeutics Ulcerative colitis Oral alpha 4 beta 7 integrin inhibitor Company switched from PTG-100 
Phase I
MORF-057 Morphic Therapeutic IBD Oral alpha 4 beta 7 integrin inhibitor Mar 2021: ph1 PD data
Source: EvaluatePharma, clinicaltrials.gov.

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