published on 04/09/2021 at 08:33
Photo credit © Sanofi Corporate
(Boursier.com) – Last-minute interim clinical data validates the ‘non-alpha’ profile of THOR-707 (SAR444245), a new experimental IL-2 from Sanofi. Interim data from a first human trial evaluating the safety, therapeutic activity and maximum tolerable dose of THOR-707 (SAR444245), an experimental highly differentiated non-alpha interleukin-2 (IL-2), as monotherapy and in combination with an anti-PD-1, will be presented in a late-breaking poster session at the American Association for Cancer Research (AACR) Annual Meeting, which will include additional updated data .
Interim data relating to safety, antitumor benefit and biomarkers validate the preclinical results. Whether in combination or monotherapy, initial efficacy was observed in patients, whether or not they had previously been treated with an anti-PD-1.
“THOR-707 could become one of the best IL-2s in its pharmacotherapeutic class and illustrates the promising potential of our Synthorin technology platform and precision biology in challenging molecular targets,” said Dr John Reed, Ph .D., Global Head of Research and Development at Sanofi. “The activity observed, whether as monotherapy or in combination with an anti-PD-1, supports the hypothesis that the unique ‘non-alpha’ profile of THOR-707 could make it an essential drug for future therapeutic combinations. in immuno-oncology. We will therefore continue to study the potential of this molecule in this perspective in order to identify the best therapeutic combinations “.
THOR-707 (SAR444245) is a modified version of IL-2, precisely PEGylated, in which the PEG chain is attached to a new amino acid introduced at an IL-2 site that prevents it from activating the alpha receptor and bind to immune receptors (IL-2R-alpha, CD25) causing drug toxicities. This modified IL-2 retains its nearly native binding to beta-gamma receptors that selectively activate effector and natural killer T cells, without causing the alpha chain-mediated immunosuppressive effects of regulatory lymphocytes or vascular leakage syndrome mediated by them. eosinophils.
Intermediate results indicate a similar pattern in which CD8 + T cells and NK cells increased after the first dose of THOR-707 and were maintained throughout the cycle, with a dose increasing effect; this effect was enhanced when combined with Keytruda (pembrolizumab). No significant increase in CD4 + regulatory T cells or eosinophils was observed, indicating selectivity for non-alpha-IL-2 receptors.
No dose-limiting toxicity was observed for THOR-707 at administered doses, up to 24? G / kg and 16? G / kg, respectively for the monotherapy and for the combined treatment. The most common post-treatment adverse events following the administration of the first dose included flu-like symptoms, fever, vomiting / nausea and chills. These symptoms were transient and disappeared after administration of standard therapy. Among the toxicities associated with G3-4, there was a transient decrease in the number of lymphocytes, which preceded the expansion of T lymphocytes.
No eosinophilia or vascular leak syndrome was reported at the doses tested. IL-5 levels remained at or below the lowest detection level, suggesting justification for the absence of IL-5 associated toxicity observed during treatment.
In addition to testing THOR-707 in combination with Keytruda and an anti-EGFR, Sanofi is separately evaluating the activity of this new biologic drug in combination with other anti-PD-1 antibodies, including Libtayo (cemiplimab-rwlc) for the treatment of different categories of tumors and with the anti-CD38 antibody Sarclisa (isatuximab) for the treatment of myeloma.
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