OSE Immunotherapeutics (OSE) Study result summary

Mechanism of action and scientific rationale

• Lusvertikimab targets the IL-7 receptor, disrupting the upstream inflammatory cascade in IBD by blocking effector T cell activation while sparing regulatory T cells.

• IL-7 and its receptor are upregulated in IBD, especially in patients resistant to standard therapies, positioning IL-7R as a marker of treatment resistance.

• Preclinical studies show lusvertikimab reduces inflammation in humanized IBD mouse models and skin inflammatory models, outperforming partial agonist antibodies.

• The antibody blocks T cell trafficking to the gut by inhibiting integrin expression, reducing T cell infiltration in the colon.

• Phase I trials in healthy volunteers demonstrated good safety, high receptor occupancy, and effective target engagement.

Phase II clinical trial results in ulcerative colitis

• The phase II trial enrolled 150 moderate-to-severe UC patients, testing 450 mg and 850 mg IV doses at weeks 0, 2, and 6.

• Both doses showed statistically significant improvement in the modified Mayo score at week 10 versus placebo, with 850 mg showing greater promise, especially in more severe patients.

• Sustained benefit was observed up to week 34, with two-thirds of patients maintaining response, including late responders.

• Endoscopic and histological improvements were significant, with treatment effects of 20–35% over placebo, considered game-changing in IBD.

• Fecal calprotectin normalization and consistent efficacy across clinical, endoscopic, and biomarker endpoints were observed.

Safety and biomarker insights

• Lusvertikimab demonstrated a favorable safety profile, with no alarming signals or significant lymphopenia in phase I and II.

• Molecular analyses confirmed effective IL-7 pathway blockade and reduction of mucosal inflammatory cells.

• Precision medicine approaches using biomarkers showed up to 60% clinical remission in biomarker-positive patients, suggesting potential to break the therapeutic ceiling.

• No increased risk of malignancy or infections was observed, and memory T and B cell repertoires remained intact.