Morphic Therapeutic (NASDAQ:MORF) today announced the presentation of new preclinical data in the MORF-057 IBD development program that are consistent with previous findings and add new support to mechanistic understanding of the molecule’s activity in a nonhuman primate (NHP) model of ulcerative colitis. The poster presentation was made at Digestive Disease Week (DDW) 2023.
“The data presented at DDW continue to refine and reinforce our understanding of the pharmacokinetic-pharmacodynamic relationship of α4β7 inhibition with respect to cellular biomarkers and MORF-057’s translation to treatment of patients. Further, these results link Morphic’s small molecule α4β7 inhibitors with the pharmacology associated with approved anti-integrin IBD treatments,” commented Bruce Rogers, PhD, President of Morphic.
The study presented at DDW examines longitudinal changes in circulating biomarkers in nonhuman primates (NHP) infused with stepwise increasing doses of MT-105, a small-molecule, selective α4β7 integrin inhibitor tool compound with similar chemical properties to MORF-057.
Key findings from the NHP study included consistency of biomarker data when compared with previous MORF-057 results and with observations from the approved monoclonal antibody α4β7 inhibitor. α4β7 inhibition with MT-105 elicits similar changes, including α4β7 receptor occupancy and lymphocyte subset changes, to those seen in humans receiving α4β7-targeted monoclonal antibodies or Morphic’s small molecule inhibitor of α4β7, MORF-057. The tool compound also demonstrates consistency of pharmacokinetic effect between individual animals with highly similar exposure response curves measuring the memory T cell biomarker. Notably, unbiased single cell RNA sequencing (scRNAseq) of pretreatment and MT-105-treated peripheral blood mononuclear cells reveals consistent increases in circulating plasma cells and plasmablasts correlated with increasing exposure of MT-105. These data suggest that α4β7 inhibition with MT-105 impacts antibody secretion related to gut inflammation.
Poster Sa1761: Predictive Translational Blood Biomarkers Dynamics of small molecule A4B7 inhibition in Nonhuman Primate
Authors: Jamie Wong, Dooyoung Lee, Huidong Chen, Maloy Mangada, Bryce Harrison, Matthew G. Bursavich, Adrian S. Ray, Bruce N. Rogers, and Blaise Lippa
Poster: DDW poster Sa176 is available on the Investors tab of Morphic’s website.
