OSE-127 – Lusvertikimab, is a monoclonal immunomodulatory antibody targeting the CD127 receptor, the alpha chain of the interleukin-7 receptor (IL-7R) that induces a powerful antagonist effect on effector T lymphocytes. Interleukin-7 is a cytokine which specifically regulates the tissue migration of human effector T lymphocytes. The blockage of IL-7R prevents the migration of pathogenic T lymphocytes while preserving regulator T lymphocytes which have a positive impact in autoimmune diseases.

• The randomized, double-blind ongoing Phase 2 clinical trial sponsored and conducted by OSE Immunotherapeutics aims to assess the efficacy and safety of OSE-127 versus placebo in patients with moderate to severe active Ulcerative Colitis (UC) who have previously failed or lost response or are intolerant to previous treatment(s).
• Besides immuno-inflammation, OSE-127 has also demonstrated great therapeutic potential in immuno-oncology through positive efficacy preclinical results in Acute Lymphoblastic Leukemia (ALL), a very aggressive tumor. Novel targeted immunotherapies are urgently needed to address relapsed/refractory (R/R) form of the disease, especially in T-ALL where the need for novel therapies is significant.

ABOUT THE OSE-127 (Lusvertikimab) CLINICAL PROGRAM

• Positive results from Phase 1 clinical study
• A Phase 2 study ongoing in Ulcerative Colitis (UC)
  
  

The Phase 1 showed a good safety and tolerability profile for OSE-127.

An article, selected as ‘Top Read’ for the March 15^th issue, was published online in ‘The Journal of Immunology’ (online). The publication, entitled “First-in-Human Study in Healthy Subjects with the Non-Cytotoxic 1 Monoclonal Antibody OSE-127, a Strict Antagonist of the IL-7Rα” reports on the Phase 1 positive results. These showed a good safety and tolerability profile for OSE-127, with no signs of significant lymphopenia, cytokine release syndrome or T-cell compartment alterations. All pharmacokinetic and pharmacodynamic parameters were consistent and demonstrated a dose-proportionality across the several dose-levels up to 10 mg/kg.  A decreased IL-7 pathway gene signature in human peripheral blood cells has been demonstrated confirming the efficient blockade of the target.

Ongoing Phase 2 clinical trial in UC with positive interim analysis

The ongoing Phase 2 trial sponsored by OSE Immunotherapeutics is evaluating the efficacy and safety of OSE-127 (Lusvertikimab) versus placebo in patients with moderate to severe active UC who previously failed or lost response or were intolerant to previous treatment(s). A positive interim futility analysis was observed in the prespecified first 50 patients (i.e., 33% of the total patient enrollment in the study) having completed the induction phase. The upcoming major milestone for this Phase 2 clinical trial is expected in December 2023 with the top-line results after the induction phase (primary endpoint at week 10) and in H1 2024 for the first early assessment in maintenance after 6 months of therapy (CoTikiS trial: NCT04882007).

UC is a debilitating and chronic inflammatory bowel disease which affects 3.3 million patients in US, Europe and Japan ⁽¹⁾ representing 12.2 per 100,000 people by year ⁽²⁾. Despite broad options, remission rates are only 25-30% ⁽³⁾ leaving most patients without satisfactory treatments. The disease is characterized by a heavy burden on patients’ lives with a strong medical need for new therapeutic options.

(1) EvaluatePharma

(2) Updated Incidence and Prevalence of Crohn’s Disease and Ulcerative Colitis in Olmsted County, Minnesota (1970-2011). Loftus EV et al. October 2014.

(3) Drugs Context. 2019; 8: 212572 –doi: 10.7573/dic.212572