On November 9, 2018 Synthorx, Inc., a biotechnology company using a first-of-its-kind Expanded Genetic Alphabet platform technology to discover and develop optimized biologics for cancer and autoimmune disorders, reported company researchers will present results of preclinical studies demonstrating the safety and anti-tumor effects of its lead product candidate THOR-707, a "not-alpha" Synthorin of interleukin-2 (IL-2), for the treatment of solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting (Press release, Synthorx, NOV 9, 2018, View Source [SID1234531204]). Marcos Milla, Ph.D., chief scientific officer of Synthorx, will present the poster on Friday, November 9, from 12:45 – 2:15 p.m. and 6:30 – 8:00 p.m. ET at the Walter E. Washington Convention Center in Washington, D.C.
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The study, titled "THOR-707: An engineered IL-2 for the treatment of solid tumors with superior preclinical efficacy and safety evidence," investigates the application of Synthorx’s Expanded Genetic Alphabet platform technology to engineer THOR-707, a variant of recombinant human IL-2 that is pegylated at one specific site and designed to kill tumor cells without inducing vascular leak syndrome (VLS), a toxicity associated with aldesleukin, an approved recombinant IL-2. Aldesleukin was approved by the U.S. Food and Drug Administration over 25 years ago for the treatment of patients with metastatic renal cell carcinoma and metastatic melanoma. However, widespread use of aldesleukin has been limited by toxicities, which include life-threatening and sometimes fatal VLS, as well as by its short half-life, requiring courses of dosing of three times per day over eight days.
In Synthorx’s preclinical studies, THOR-707 induces molecular markers of T cell activation and the proliferation of peripheral NK and CD8+ effector T cells in vivo. However, dosing of THOR-707 has minimal effect on molecular and clinical markers of VLS, even at high exposures. Analysis of the effect of THOR-707 in syngeneic mouse tumor models showed that THOR-707 induced infiltration of CD8+ T effector cells into tumors and elicited anti-tumor effects alone and in combination with a PD-1 immune checkpoint inhibitor.