TSHR

- 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, Mich., Sept. 25, 2023 /PRNewswire/ -- 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 . 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 . Investor Contact Jessica Vo Gilmartin Group, LLC [email protected] Media Contact Adam Daley Berry & Company Public Relations 212.253.8881 [email protected] SOURCE Sling Therapeutics

Results highlighted in oral presentation show linsitinib significantly limited disease severity in early- and late-stage TED mouse models and prevented development of autoimmune response Company currently evaluating linsitinib in ongoing global Phase 2b LIDS clinical trial in patients living with active, moderate to severe TED ANN ARBOR, Mich., Sept. 11, 2023 /PRNewswire/ -- 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 presentation of preclinical data demonstrating that treatment with linsitinib, an investigational small molecule insulin-like growth factor I receptor (IGF-1R) inhibitor, significantly limited disease severity in TED mouse models in early and late stages of the disease as well as prevented the development of autoimmune responses. The data are being highlighted today in an oral presentation at the 45th Annual Meeting of the European Thyroid Association (ETA) being held September 9-12, 2023, in Milan, Italy. "We are pleased to have the opportunity to highlight the latest data from our linsitinib development program at the ETA Annual Meeting, which add to a growing body of evidence indicating its potential to be an effective, novel first-line oral treatment for people suffering from TED at all stages," said Ryan Zeidan, Ph.D., President and Chief Executive Officer of Sling Therapeutics. "We look forward to further assessments of linsitinib as we continue to enroll people living with TED in our ongoing global Phase 2b LIDS clinical trial." In the preclinical study, researchers evaluated mice immunized with a plasmid encoding the A-subunit of thyroid stimulating hormone receptor (TSHR) that were orally administered linsitinib for four weeks. An autoimmune response against TSHR induces Graves' disease, of which TED is a common manifestation. Results showed that treatment of immunized mice with linsitinib after disease onset significantly limited the severity of the disease in both early and late stages of the disease. Treatment with linsitinib also prevented development of an autoimmune response including autoimmune hyperthyroidism, morphological changes, formation of brown adipose tissue in the orbita, and orbital immune cell infiltration into the orbit in all stages of TED in mouse models. Sling Therapeutics is currently enrolling participants in the ongoing Phase 2b LIDS clinical trial, a global, randomized, double-mask, placebo-controlled study designed to evaluate the safety, pharmacokinetics and efficacy of linsitinib in patients with active, moderate to severe TED over 24 weeks of treatment. Participants are being enrolled at trial sites in the United States, Canada, Italy, Spain, and the UK. For more information about the Phase 2b LIDS trial, visit . 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. TED is characterized by excess fibrous tissue growth behind the eyes, and this 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 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 . Investor Contact Jessica Vo Gilmartin Group, LLC [email protected] Media Contact Adam Daley Berry & Company Public Relations 212.253.8881 [email protected] SOURCE Sling Therapeutics

Less than half of Graves' Disease patients achieve remission with anti-thyroid drugs, and nearly half of those that do will relapse. NEWTON, Mass., Aug. 16, 2023 /PRNewswire/ - Graves' Disease (GD) is an autoimmune disease and the leading cause of overactive thyroid. For the last several decades, the GD treatment landscape has included three main options: Anti-thyroid drugs (methimazole and propylthiouracil) Radioiodine ablation Thyroidectomy The majority of GD patients elect for anti-thyroid drugs (ATDs) as first-line because it is the only non-definitive treatment option and can also induce and sustain remission off therapy, although less than half of patients will successfully achieve this outcome. Patients who relapse can opt for another round of ATDs or choose a definitive option like radioiodine ablation or surgery – both of which irreversibly destroy the thyroid gland and require patients to take lifelong thyroid hormone replacement therapy. According to REACH Market Research 's MarketVue® assessment, endocrinologists are eager for novel, targeted therapeutics for GD that do not irreversibly destroy the thyroid gland. Endocrinologist, U.S.— "Patients want a treatment, and we do too, that targets the source of the problem, which is the antibody to the TSH receptor, rather than treating the downstream consequences with some fairly extreme options." To access REACH's MarketVue® Report on GD, visit or contact us at [email protected]. Despite high disease prevalence of GD (over 75,000 newly diagnosed cases per year in the US), the pipeline remains sparse with only a few biologics in early-stage development, including: Immunovant's FcRn monoclonal antibody, batoclimab, which recently initiated a Phase 2 trial Anti-TSHR monoclonal antibodies, peptides, and antagonist small molecules that are in preclinical stages or early Phase 1 trials Tyler Jakab, Analyst at REACH: "Graves' patients hope for disease remission off ATD therapy, but relapse rates remain high. The introduction of another therapy may offer an additional opportunity for remission among those who relapse and are otherwise hesitant to undergo a definitive treatment like ablation or surgery." About MarketVue® MarketVue® reports are a rare disease focused, fresh alternative to traditionally long and outdated market research reports. MarketVue® reports cover rare disease epidemiology and key market dynamics based on research from key opinion leader interviews, physician surveys, and secondary data. About REACH Market Research REACH is an independent pharmaceutical market research company focused on rare and niche diseases. With decades of experience in pharmaceutical market research and life sciences consulting, REACH fills an important gap in the market – accessible market research solutions for rare and niche diseases. SOURCE REACH Market Research