Applied Molecular Transport Inc. announced top-line Phase 2 results from the MARKET combination trial for AMT-101 in biologic-naïve patients with moderate-to-severe UC. AMT-101 is an investigational, once-daily, GI-selective, oral fusion of IL-10 and AMT's proprietary carrier molecule. In the MARKET trial, patients received either once-daily oral AMT-101 3mg in combination with adalimumab (sub-cutaneous administration per the approved UC label), or adalimumab alone (with placebo).

The objectives of the MARKET trial were to assess the safety and efficacy of AMT-101 in combination with anti-TNFa therapy (adalimumab) in patients with moderate-to-severe UC. The key efficacy endpoint of clinical remission was measured at 8 weeks. The clinical remission rate in the adalimumab alone arm was higher than historical anti-TNFa monotherapy benchmarks, and the data from the MARKET trial did not demonstrate added clinical benefit in the combination arm compared to the adalimumab alone arm at week 8. Of the 49 evaluable patients, 31.8% (7/22) of patients treated in the combination arm (AMT-101 3mg with adalimumab) achieved clinical remission versus 33.3% (9/27) in patients receiving adalimumab alone at week 8. Clinical remission is defined as Mayo endoscopic subscore of 0 or 1, rectal bleeding subscore of 0 and stool frequency subscore of 0 or 1. AMT-101 appeared safe and well-tolerated.

Treatment emergent adverse events (TEAEs) were mostly mild to moderate, with one serious adverse event (SAE) observed, worsening of UC, which was determined to be unrelated to study treatment. Overall patient demographics were balanced between the two arms with the exception of patients in the combination arm having much shorter duration of UC history versus patients in adalimumab alone arm. Based on this observation, conducted a post hoc sub-group analysis to explore the potential effect of duration of UC history on clinical remission.

Sub-group analysis revealed that patients with a shorter duration of UC (< 5 years) had clinical remission rates of 43.8% (7/16) in the combination arm versus 15.4% (2/13) in the adalimumab alone arm. In patients with longer duration UC (= 5 years), clinical remission rates were 0.0% (0/6) in the combination arm versus 50.0% (7/14) in patients receiving adalimumab alone. AMT anticipates a number of milestones for its AMT-101 development program in IBD.

For chronic pouchitis, FDA has granted an end of Phase 2 meeting for AMT-101 to discuss Phase 3 development. The company also anticipates top-line results from its ongoing AMT-101 Phase 2 LOMBARD monotherapy trial for UC in the second half of 2022.