– Linsitinib inhibited the formation of CD4+ T-cells in bone marrow, which are upregulated and clinically relevant in Thyroid Eye Disease (TED) –
– Ongoing global Phase 2b LIDS clinical trial evaluating linsitinib for treatment of active, moderate to severe TED will provide clinical context and relevance –
Ann Arbor, MI, September 25, 2023 — Sling Therapeutics, Inc., a biopharmaceutical company focused on late-stage development of an oral small molecule for the treatment of thyroid eye disease (TED), today announced the publication of new preclinical data demonstrating linsitinib reduced pathologic bone marrow activity in a mouse model of TED. The data have been published in the peer-review journal Frontiers in Endocrinology.
“As TED develops in patients, autoreactive CD4+ T-cells migrate into the bone marrow, inducing activation of the bone marrow and consecutive myelopoiesis. These latest preclinical data showed treatment with linsitinib significantly inhibited the activation pathway by blocking myeloid cells traveling to the thyroid and orbit, and directly induced arginase-1 in the bone marrow, leading to a depletion of arginine,” said Anja Eckstein, M.D., professor and head of the Department of Orthoptics, Oculoplastic and Reconstructive Surgery and Orbital Center at the University Eye Hospital Essen, Germany. “Given that T-cells require arginine to activate and proliferate properly, the number of CD4+ T-cells in the bone marrow significantly decreased following treatment with linsitinib, resulting in reduced inflammation and tissue damage.”
“This recent dataset reinforces Sling’s deep commitment to preclinical work designed to better elucidate the role of linsitinib as a potential first-line oral drug to treat all stages of TED,” said Jeffrey Kent, M.D., Chief Medical Officer of Sling Therapeutics. “Abnormal bone marrow activity has been implicated in multiple autoimmune diseases, where the role of cytokine production via increased hematogenesis exacerbates clinical disease. We are pleased to be among first to demonstrate the effect of IGF-1R inhibition on this process and we are even more delighted to demonstrate that linsitinib markedly reduces pro-inflammatory cytokines which are released due to upregulated activity of hematopoietic stem and progenitor cells (HSPC). We look forward to translating these preclinical results in our ongoing global Phase 2b LIDS trial.”
The preclinical study investigated the effect of linsitinib on bone marrow activity in mice immunized with a plasmid encoding the A-subunit of thyroid stimulating hormone receptor (TSHR). Analyses of treated bone marrow showed downregulation of multiple cytokines associated with TED and upregulation of arginase-1.
For more information about the Phase 2b LIDS trial, visit https://clinicaltrials.gov/ct2/show/NCT05276063.
About Thyroid Eye Disease (TED)
TED is a debilitating autoimmune disease that affects about 20,000 people in the U.S. per year and has a similar prevalence in Europe. Dysfunction in the IGF-1R signaling pathway leads to a prevalence of thyroid-stimulating hormone receptor autoantibodies (TSHR-Abs) that drive excess fibrous tissue growth behind the eyes. The inflammation can push the eyes forward or cause the eyes and eyelids to become red and swollen. As the disease progresses it can lead to pain, eye bulging, and double vision. TED predominantly affects women, and most frequently affects people with hyperthyroidism due to Graves’ disease.
About Sling Therapeutics
Sling Therapeutics, Inc., is a biopharmaceutical company focused on late-stage development of an oral small molecule for the treatment of thyroid eye disease (TED). The company is advancing the evaluation of its lead product candidate, linsitinib, in a Phase 2b clinical trial based on extensive preclinical and clinical data. Linsitinib offers the potential of a convenient oral small molecule that could significantly reduce the treatment burden for people living with TED. For more information visit https://slingtx.com/.
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