TSHR

NEW YORK, Oct. 29, 2024 (GLOBE NEWSWIRE) -- Immunovant, Inc. (Nasdaq: IMVT), a clinical-stage immunology company dedicated to enabling normal lives for people with autoimmune diseases, today announced that data from the Phase 2a trial of batoclimab in Graves’ disease will be the subject of an oral presentation of a late-breaking abstract accepted for the 2024 American Thyroid Association (ATA) Annual Meeting being held October 30 to November 3, 2024, in Chicago, Illinois. New data highlighting both thyroid-specific and extrathyroidal manifestations of Graves' disease will be presented. Late-Breaking Oral Presentation Details: Title:Efficacy and Safety of the FcRn Inhibitor, Batoclimab, in Graves’ Thyroidal and Extrathyroidal Disease: a Proof-of-concept StudyPresentation:#0020Session:#5 – Autoimmune Thyroid DiseaseDate and Time:Friday, November 1, 2024, 4:05pm – 5:05pm ETPresenter:George Kahaly, MD, PhD About Graves’ disease Graves’ disease is an autoimmune disorder associated with the overproduction of thyroid hormones and is the most common cause of hyperthyroidism. Although Graves’ disease can affect any age group or gender, it occurs often in women younger than 40 years of age. In Graves’ disease, harmful IgG autoantibodies bind to and activate the thyroid-stimulating hormone receptor present on the thyroid gland, stimulating excess thyroid hormone production. Existing treatments, which include antithyroid drugs, radioactive iodine, and thyroid surgery, are aimed at reducing thyroid hormone levels to lessen the severity of symptoms. These treatments have remained largely unchanged for the past 70 years. About Immunovant, Inc. Immunovant, Inc. is a clinical-stage immunology company dedicated to enabling normal lives for people with autoimmune diseases. As a trailblazer in anti-FcRn technology, the Company is developing innovative, targeted therapies to meet the complex and variable needs of people with autoimmune diseases. For additional information on the Company, please visit immunovant.com. Contact:Renee Barnett, MBA Chief Financial Officer Immunovant, Inc. info@immunovant.com Source: Immunovant, Inc.

Septerna just entered the clinic, and its lack of human data makes it an outlier among the companies able to successfully go public this year in what is still a cautious biotech IPO market. What the young company does have is technology based on research from a Nobel laureate and a lead drug candidate that could offer a key advantage over other treatments for a rare, inherited disease. Now it has $288 million in IPO cash to support its pipeline. Late Thursday, Septerna priced its offering of 16 million shares at $18 apiece, going beyond the preliminary financial terms it previously set. Those shares will trade on the Nasdaq under the stock symbol “SEPN.” South San Francisco-based Septerna will use most of the IPO proceeds to continue clinical testing of SEP-786 for hypoparathyroidism, an inherited deficiency of parathyroid hormone (PTH). This hormone regulates calcium and phosphate levels in the blood. Lacking this hormone leads to fatigue, brain fog, and muscle weakness. In more severe cases, patients can develop cardiovascular problems and renal failure. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum Standard hypoparathyroidism treatment includes calcium and vitamin D supplements, which do not address all of the disease’s symptoms. Takeda Pharmaceutical’s Natpara, an engineered version of parathyroid hormone, will cease production by the end of the year due to manufacturing issues. In August, the FDA approved Ascendis Pharma’s Yorvipath, the first in what could be wave of new injectable peptide hypoparathyroidism drugs. Septerna takes a different approach to the disease with SEP-786, a small molecule that targets and activates the parathyroid hormone 1 receptor (PTH1R), sparking it to produce more of the key hormone. As an oral drug, SEP-786 would offer patients less burdensome dosing. “Hormone replacement with injectable PTH peptides, either marketed or in clinical development, may improve blood chemistry profiles of patients via PTH1R activation but will require lifelong daily injections,” Septerna said in the IPO filing. “We believe there is a substantial opportunity for an oral small molecule therapy that offers convenience, improved compliance, and potentially superior efficacy.” PTH1R is a G protein coupled-receptor (GPCR), part of a family of receptors that regulate a wide range of physiological processes. The role of these receptors in both health and disease is known, and many of them are targeted by FDA-approved drugs. However, an estimated 75% of GPCR targets remain undrugged, Septerna said in the filing. Septerna’s platform technology enables scientists to isolate a GPCR and study it outside of a cell, but in a way that replicates what happens to that receptor inside a cell. With this greater understanding of GPCRs, the company designs, screens for, and optimizes small molecules that target the receptors. This technology platform, called Native Complex, is based on the research of Robert Lefkowitz, a Duke University professor of biochemistry and chemistry who was awarded the 2012 Nobel Prize in Chemistry for his work in the GPCR field. In animal tests, Septerna reported its small molecule agonists activated PTH1R and regulated key genes important for calcium homeostasis in manner similar to native parathyroid hormone. A placebo-controlled Phase 1 study will evaluate the safety and tolerability of once-daily and twice-daily dosing of the SEP-786 in healthy volunteers. The first patient was dosed last month. Preliminary data are expected in mid-2025. Sponsored Post What Healthcare Can Learn from Costco The path forward is clear: employers must evaluate their health plan the same way they do their Saturday shopping excursion. By Jeff Bak, Imagine360 CEO and President The Septerna pipeline includes two preclinical negative allosteric modulators. SEP-631 is in development for immunology and inflammation indications, such as the skin disease chronic spontaneous urticaria. TSHR has potential applications in endocrinology. Native Complex has also yielded small molecule agonists of the GLP-1, GIP, and glucagon receptors for the potential treatment of metabolic disorders. An oral Septerna drug that hits one or more of these receptors could put the biotech in competition with commercialized injectable peptide drugs, such as Eli Lilly’s Zepbound and Novo Nordisk’s Wegovy. But Septerna will likely aim to stand out from the next wave of metabolic medications in development as pills. This competition includes Structure Therapeutics, whose small molecules come from its own GPCR platform technology (when Structure went public last year, it snagged the fitting stock symbol “GPCR”). Lead Structure drug candidate GSBR-1290 is currently in mid-stage clinical development for type 2 diabetes and obesity. Since Septerna’s inception in 2019, the company had raised $224.2 million prior to the IPO, most recently a $150 million Series B round last year led by RA Capital Management. That firm holds a 7.7% post-IPO stake in Septerna, according to the prospectus. Third Rock Ventures is Septerna’s largest shareholder with a 23.6% post-IPO stake. Septerna is led by CEO Jeff Finer, who is also a venture partner at Third Rock. Septerna’s plans resonated with investors, whose interest in the biotech’s stock enabled the company to boost the IPO size twice. In preliminary financial terms set at the beginning of the week, Septerna planned to offer more than 10.9 million shares in the range of $15 to $17 each, which would have raised $175 million at the pricing midpoint. On Thursday, the biotech boosted the deal size to more than 15.2 million shares priced at $18 apiece, which would have raised $275 million at the pricing midpoint. Late Thursday, the biotech again revised the terms upward, boosting the deal to $288 million. As of the end of the second quarter of this year, Septerna reported its cash position was $155.7 million. Following the IPO, the company plans to spend $54 million to advance lead drug candidate SEP-786 through Phase 2 testing in hypoparathyroidism, according to the filing. The company also plans to use the capital to develop additional molecules that target the parathyroid hormone receptor. Another $24 million will support the completion of Phase 1 testing of SEP-631 and additional molecule inhibitors that could be potential treatments for chronic spontaneous urticaria. And $41 million is set aside for other R&D, including Septerna’s TSHR and incretin receptor programs.

Oral, small molecule parathyroid hormone 1 receptor (PTH1R) agonist maintained serum calcium control over 28-day dosing in a preclinical hypoparathyroidism model PTH1R program for hypoparathyroidism expected to enter Phase 1 in late 2024 Oral, thyroid stimulating hormone receptor (TSHR) antagonist improved thyroxine (T4) hormone levels and histological parameters associated with Graves’ disease in a preclinical model SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Septerna, a biotechnology company discovering and advancing novel, oral small molecule medicines targeting G protein-coupled receptors (GPCRs), today presented preclinical data from the company’s parathyroid hormone 1 receptor (PTH1R) program and its thyroid stimulating hormone receptor (TSHR) program which validate the application of the Native Complex Platform™ for drug discovery in endocrine disorders. The data were presented in two poster presentations and a rapid-fire oral presentation during the Endocrine Society’s Annual Meeting (ENDO 2024) held June 1-4, 2024, in Boston, MA. Data from the PTH1R program showed small molecule agonists of PTH1R engaged endogenous pathways in the kidney and bone similar to native PTH peptide and demonstrated sustained control of serum calcium and phosphate levels over 28 days with daily oral administration. These results suggest that oral small molecule PTH1R agonists may be suitable alternatives to injectable PTH peptides for the treatment of hypoparathyroidism. The company plans to initiate a Phase 1 trial with its lead PTH1R agonist candidate in healthy volunteers in late 2024. “Our PTH1R agonist is the only small molecule in development to behave similarly to native PTH, and we are excited about its potential to reshape the treatment paradigm for hypoparathyroidism as we advance into the clinic later this year,” said Jeffrey Finer, M.D., Ph.D., Chief Executive Officer and Co-founder of Septerna. “We are also pleased to showcase data from our TSHR antagonist program demonstrating its ability to target the known drivers of Graves’ disease, an indication for which there are currently no disease-modifying oral small molecules. Together, these data validate the ability of our Native Complex Platform™ to unlock difficult-to-drug GPCRs and to discover novel small molecules to address numerous endocrine disorders.” Summary of PTH1R Data The rapid-fire oral presentation and poster, entitled “Characterization of a Novel Oral Small Molecule PTH1R Agonist: Proof of Concept for an Alternative to Injectable Peptide-based Therapy for Hypoparathyroidism,” were presented by Jun Zhang, Ph.D., Senior Director of Disease Biology for Septerna. To assess PTH1R engagement in key target tissues, primary tissue from the renal cortex and tibial bone was assessed following in vivo treatment with PTH peptide and Septerna’s small molecule PTH1R agonist. The results suggest that PTH1R-regulated genes were similarly impacted by both PTH peptide and small molecule agonists. Oral administration of a single dose of Septerna’s PTH1R agonist in a surgical rat model that mimics hypoparathyroidism in patients resulted in significant upregulation of serum calcium levels for a period of 24 hours in a dose dependent manner. The data also demonstrated sustained control of serum calcium and phosphate levels over 28 days with daily oral administration. The window of calcium upregulation is comparable to injectable PTH peptides currently in development to treat hypoparathyroidism. Summary of TSHR Data Additionally, a poster entitled “A Novel, Oral Small Molecule Antagonist Targeting TSHR Improves Hyperthyroidism in an in vivo Model of Graves’ Disease” was presented. Data from the TSHR program demonstrated that Septerna’s small molecule TSHR antagonist blocks the stimulating effects of autoantibodies known to drive Graves’ disease (GD). Sustained treatment with the TSHR antagonist reduced the overall size of the thyroid gland and improved histological parameters associated with GD, providing proof-of-concept that potent small molecules directly targeting TSHR function have the potential to ameliorate the effects of hyperthyroidism in GD. The company is advancing several lead molecules toward the selection of a development candidate for GD and Graves’ ophthalmopathy (also known as thyroid eye disease or TED). About Septerna Septerna, Inc. is a biotechnology company focused on advancing novel, oral small molecule medicines targeting the entire class of G protein-coupled receptors (GPCRs). The company’s Native Complex Platform™ recapitulates GPCRs with their native structure, function, and dynamics outside of the cellular environment to rapidly apply new technologies for industrial-scale drug discovery to address both validated GPCRs and many GPCRs that have been undruggable and unexploited to date. Septerna is building a pipeline of GPCR-targeted, oral small molecule drug candidates, led by its program targeting the parathyroid hormone 1 receptor (PTH1R) for the treatment of hypoparathyroidism. Septerna was launched in 2022 by scientific founders who have made groundbreaking GPCR discoveries. For more information, please visit . About the PTH1R Program and Hypoparathyroidism Septerna is developing a novel, first-in-class, oral small molecule parathyroid hormone 1 receptor (PTH1R) agonist designed to treat patients with hypoparathyroidism, a harmful condition characterized by a deficiency of the parathyroid hormone (PTH). Hypoparathyroidism results in a wide range of debilitating symptoms, including fatigue, brain fog, muscle weakness, tissue calcification, and in severe cases can lead to seizures, heart arrhythmias, and kidney failure. Current available treatments include supplements that only partially address PTH deficiency, or PTH peptide replacements, which require daily injections. Septerna’s investigational PTH1R agonist has been shown to normalize serum calcium levels in preclinical studies and has the potential to be the first oral alternative to injectable treatments for hypoparathyroidism. About the TSHR Program and Graves’ disease Septerna is developing a novel, investigational, oral small molecule thyroid stimulating hormone receptor (TSHR) antagonist for the treatment of Graves’ disease and thyroid eye disease (TED). Graves’ disease is an autoimmune condition in which the body produces antibodies that bind to and activate the TSH receptor on thyroid cells. These antibodies stimulate the thyroid gland to produce too much thyroid hormone, resulting in hyperthyroidism. Additionally, in TED, the antibodies stimulate TSH receptors on cells behind the eyes, causing swelling of the eye muscles, which can result in eye bulging, pain and impaired vision. Current standard-of-care treatments for Graves’ disease are inadequate and focus on the thyroid (surgery, radioactive iodine, and antithyroid medicines) while failing to prevent progression to TED. Septerna’s TSHR program is designed to block the activity of all Graves’ autoactivating antibodies as a single oral therapeutic.