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Interim recent clinical data confirm the non-alpha profile of THOR-707 (SAR444245), Sanofi’s new IL-2 investigator.
Interim recent clinical data confirm the non-alpha profile of THOR-707 (SAR444245), Sanofi’s new IL-2 investigator. Early clinical results are consistent with preclinical studies and suggest that THOR-707 (SAR444245) may promote an anti-tumor immune response without alpha-mediated side effects, either alone or in combination with anti-PD-1 THOR-707, precisely modified with PEG – a modified version of IL-2, developed on Sanofi Synthorin ™ technology platform, is being studied in a trial of adults with enlarged or metastatic solid tumors PARIS – April 9, 2021 – Interim data from the first human trial evaluating safety, therapeutic activity and maximum tolerated dose of THOR- 707 (SAR444245), a highly differentiated non-alpha interleukin-2 (IL-2) candidate as monotherapy and in combination with anti-PD-1, will be presented Saturday, April 10, as a final poster presentation at the American Research Association Annual Meeting cancer (AACR). On Saturday night, the poster session will include additional updates. Interim data on safety, antitumor activity and biomarkers further support the preclinical profile of non-alpha-IL-2. Both in combination and in monotherapy conditions, initial activity was observed with three confirmed partial responses, which include patients who had previously received anti-PD-1 therapies. “THOR-707 has a potentially best-in-class profile and reinforces the promise of our Synthorin technology platform to overcome challenging targets with precision biology,” said John Reed, MD, head of global research and development at Sanofi. “The activity seen both as a single agent and in combination with anti-PD-1 further reinforces our belief that, as a unique non-alpha-IL-2, THOR-707 could form the basis of future immuno-oncological therapies. … We will continue our research. the potential of the molecule for better combinations in disease. ” THOR-707 is a precisely pegylated version of IL-2, where a PEG chain is attached to a new amino acid inserted in place on IL-2, which prevents it from interacting with the alpha receptor and binding to immune receptors that cause drug toxicity. (IL-2R-alpha, CD25). Engineered IL-2 retains close-to-native binding to beta-gamma receptors that selectively proliferate tumor-killing effector T cells and natural killer (NK) cells without alpha-mediated immunosuppressive effects regulatory T cells or vascular leakage syndrome eosinophil mediated. Interim results indicate a similar pattern where CD8 + T and NK cells increased after the first dose of THOR-707 and persisted throughout the cycle, with the effect of increasing the dose; this effect was enhanced when combined with KEYTRUDA® (pembrolizumab). There was no significant increase in CD4 + regulatory T cells or eosinophils, suggesting selectivity for the non-alpha IL-2 receptor. No dose limiting toxicity was observed for THOR-707. in the stated doses up to 24 μg / kg as monotherapy and 16 μg / kg in combination. The most common treatment-related side effects (ADEs) after the first dose included flu-like symptoms, fever, vomiting / nausea, and chills. Symptoms were temporary and resolved with standard maintenance therapy. Among the toxic effects associated with G3-4 was a transient decrease in lymphocyte count that preceded T cell expansion. No eosinophilia or vascular leak syndrome has been reported at any dose tested. IL-5 levels remained at or below the lowest detection level, suggesting an explanation for the lack of IL-5-related toxicity observed during treatment. “New approaches such as non-alpha IL-2 are aimed at activating this powerful immune pathway while mitigating current dosing and safety concerns to potentially expand the population of patients who can benefit from treatment,” said Philip Jancu, MD. sciences. , Assistant Professor, Department of Investigative Cancer Therapy, Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX. “Preclinically, THOR-707 appeared to activate an anti-tumor immune response without an increased risk of alpha-mediated toxicity such as eosinophilia or vascular leakage syndrome. Although early on, the interim clinical data in AACR are very close to what we have seen in preclinical studies and suggest that further study of this non-alpha IL-2 molecule is needed, either alone or in combination with synergistic treatments. such as anti-PD- 1. ”The dose escalation of THOR-707 went beyond the predicted RP2D monotherapy from 24 µg / kg Q3W to 32 µg / kg Q3W to further characterize the upper end of the dose range. In addition to testing THOR-707 in combination with KEYTRUDA, Sanofi plans to evaluate the activity of this new biological drug in combination with other anti-PD-1 antibodies, including Libtayo®1 (cemiplimab) anti-CD38 antibody, Sarclisa® (isatuximab). ) and anti-EGFR. Editor’s Note: Sanofi previously entered into an agreement with Merck & Co. Inc., Kenilworth, NJ, USA (known as MSD outside the USA and Canada) to conduct a Phase 2 trial of THOR-707 in combination with KEYTRUDA or sequentially. … About THOR-707 (SAR444245) THOR-707 is a modified PEGylated version of IL-2 with an extended half-life that is being investigated for the treatment of many types of malignant neoplasms. In addition, pharmacology is being evaluated to determine if THOR-707 can tolerate less frequent dosing. In preclinical experiments, THOR-707 has demonstrated the ability to induce the growth of CD8 + T cells, which indicates the potential for antitumor effects both as a single agent and in combination with an anti-PD-1 monoclonal antibody. THOR-707 is not approved by any regulatory body. THOR-707 is the first molecule from the Synthorin ™ technology platform. Sintorins are new proteins built on Sanofi’s unique extended genetic alphabet platform that enables scientists to fill important gaps in protein therapy by significantly expanding the variety of building blocks available to bioengineers. The Expanded Genetic Alphabet platform, used alone or in combination with other Sanofi technologies, allows the company’s scientists and bioengineers to develop new biologics for the treatment of cancer and other diseases. About Sanofi Sanofi is committed to supporting people in solving their health problems. We are a global biopharmaceutical company focused on human health. We prevent disease with vaccines, offer innovative treatments for pain and alleviate suffering. We support the few who suffer from rare diseases and millions of people with long-term chronic diseases. With more than 100,000 people in 100 countries, Sanofi is transforming scientific innovation into healthcare solutions around the world. 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