P421 SER-287, an investigational microbiome therapeutic, induces remission and endoscopic improvement in a placebo-controlled, double-blind randomised trial in patients with active mild-to-moderate ulcerative colitis

Faecal microbiota transplants provide proof-of-concept that manipulation of the gut microbiome can provide therapeutic benefits in patients with ulcerative colitis (UC). SER-287, an ecology of Firmicute bacterial spores, is postulated to decrease gut inflammation by modifying the microbiome composition. We conducted a phase 1b trial of SER-287 in 58 adults with mild-to-moderate UC. Patients were assigned to 1 of 3 SER-287 treatment arms or placebo. SER-287 treatment arms included 6 days of vancomycin pre-treatment followed by 8 weeks of SER-287 either daily or weekly and placebo pre-treatment followed by weekly SER-287. Efficacy outcomes included remission (total modified Mayo score [TMMS] ≤2 and endoscopic subscore ≤1), endoscopic improvement (decrease in endoscopic subscore ≥1), clinical response (decrease of ≥3 points in TMMS, with EITHER decrease of ≥1 point in rectal bleeding OR absolute rectal bleeding of 0 of 1) and were assessed, along with safety and tolerability of SER-287 by standard safety measures. Microbiome engraftment was longitudinally assessed by whole metagenomic sequencing. Remission and endoscopic improvement, intent to treat (ITT) population. Remission occurred in 40% (6 of 15) receiving vancomycin pre-treatment followed by SER-287 daily (Vanco/SER-287 QD) and in 0% receiving placebo (p = 0.024, see Figure 1). Endoscopic improvement occurred in 40% (6 of 15) in the Vanco/SER-287 QD arm and in 9% (1 of 11) receiving placebo (not significant). The weekly dosing arms had remission and endoscopic improvement rates intermediate between the Vanco/SER-287 QD and PBO arms, consistent with a dose-dependent effect. Engraftment of SER-287 bacteria was greatest in the Vanco/SER-287 QD compared with other SER-287 treatment or placebo arms. Furthermore, SER-287 bacteria were more prevalent across subjects who achieved remission as compared with those who were not remitters. Safety of SER-287 was comparable to placebo. Gastrointestinal (GI) AEs were most frequent; the Vanco/SER-287 QD arm experienced the lowest percentage of GI AEs, likely reflecting decreased UC disease activity. SER-287 daily for 8 weeks was safe and well tolerated and provides a significant effect in induction of remission in active mild-to-moderate UC patients. Microbiome alterations were consistent with a mechanism of action of engraftment preceding a clinical effect. SER-287 may provide a safe and efficacious oral non-immunosuppressive therapy, addressing an unmet medical need in UC, warranting continued clinical development.