amylin

Topline GSBR-1290 Phase 2a 12-week obesity data, as well as data from formulation bridging and titration optimization study, on track for latter half of the second quarter 2024 Phase 2b study in obesity expected to begin as planned in the fourth quarter 2024 Year-end cash balance of $467.3 million expected to fund operations and key clinical milestones through 2026 SAN FRANCISCO, March 08, 2024 (GLOBE NEWSWIRE) -- Structure Therapeutics Inc. (NASDAQ: GPCR), a clinical-stage global biopharmaceutical company developing novel oral small molecule therapeutics for metabolic and cardiopulmonary diseases, today reported financial results for the fourth quarter and full year ended December 31, 2023, and highlighted recent corporate achievements. “In 2023 we demonstrated clear proof-of-concept with our lead GLP-1 receptor agonist, GSBR-1290, for obesity and type 2 diabetes. As a differentiated oral small molecule we have the scalability and manufacturing advantages to potentially meet the significant unmet need currently observed in the GLP-1 space,” said Raymond Stevens, Ph.D., Founder and CEO of Structure Therapeutics. “With a year-end cash balance of $467.3 million providing runway through the end of 2026, we are well-positioned to initiate and complete our Phase 2b trials for GSBR-1290 and accelerate development of our oral small molecule programs targeting amylin, GIP, and apelin receptors.” Recent Highlights and Upcoming Milestones GSBR-1290 for Type 2 Diabetes Mellitus (T2DM) and Obesity In December 2023, the Company reported clinically meaningful data from the Phase 2a study in T2DM demonstrating significant reductions in hemoglobin A1c (HbA1c) and weight at 12 weeks. Interim Phase 2a data from the obesity cohort demonstrated significant reduction in weight at 8 weeks. Across both cohorts, GSBR-1290 was generally well-tolerated with no treatment-related serious adverse events over 12 weeks and low study discontinuation rates due to adverse events related to study drug (2.8% in T2DM and 0% in obesity).Topline data from the obesity cohort of the Phase 2a study, including full 12-week efficacy data for 40 participants and safety and tolerability for all 64 participants. This study is fully enrolled and data are expected in the latter half of the second quarter of 2024.In preparation for later stage clinical trials, a formulation bridging and titration optimization study to evaluate capsule versus tablet pharmacokinetics (PK) and explore different titration regimens of GSBR-1290 is ongoing. This study is fully enrolled and data are expected in the latter half of the second quarter of 2024.The Company plans to initiate a global Phase 2b obesity study of GSBR-1290 in the fourth quarter of 2024.The Company plans to initiate a Phase 2 study in T2DM in the second half of 2024. GLP-1R Combination Programs: Amylin, GIPR, Apelin (APJR) Oral Small Molecule Amylin Program: The Company is developing amylin agonists for use either alone or in combination with GLP-1R agonists to treat obesity and associated diseases, and expects to select a development candidate in the second half of 2024.Oral Small Molecule GIPR Program: The Company is developing a GIPR selective agonist and GLP‑1R/GIPR combinations to treat obesity and associated diseases, and expects to select a development candidate in the first half of 2025.Oral Small Molecule Apelin Receptor (APJR) Program: The Company is evaluating its Phase 2 ready ANPA-0073, a biased agonist targeting APJR used in combination with weight loss medicines, for selective or muscle-sparing weight loss. ANPA-0073 is also being evaluated for idiopathic pulmonary fibrosis (IPF). The Company has completed a Phase 1 single-ascending and multiple-ascending dose study, in which ANPA-0073 was generally well-tolerated with no serious adverse event reported. LPA1R Program for Idiopathic Pulmonary Fibrosis (IPF) The Company is developing LTSE-2578, an oral small molecule antagonist that targets lysophosphatidic acid 1 receptor (LPA1R). Preclinical studies have demonstrated substantial anti-fibrotic activity in mouse models of fibrotic lung disease, and the Company expects to initiate a first-in-human study of LTSE-2578 in the second quarter of 2024. Corporate In 2023, the Company raised approximately $485.0 million of equity capital: $185.0 million in gross proceeds from the initial public offering in February, and $300.0 million in gross proceeds from the private placement equity financing in October. Fourth Quarter and Full Year 2023 Financial Highlights Cash Position: Cash, cash equivalents and short-term investments totaled $467.3 million at December 31, 2023. The Company expects its current cash, cash equivalents and short-term investments to fund operations and expected key clinical milestones through at least 2026. R&D Expenses: Research and development (R&D) expenses for the fourth quarter of 2023 were $20.0 million, as compared to $8.4 million for the same period in 2022. For the year ended December 31, 2023, R&D expenses were $70.1 million, as compared to $36.2 million for the full year 2022. The increase was primarily due to the advancement of the Company’s GLP-1R franchise and other research programs, clinical study activities and increases related to employee expenses, primarily due to an increase in personnel. G&A Expenses: General and administrative (G&A) expenses for the fourth quarter of 2023 were $11.0 million, as compared to $4.6 million for the same period in 2022. For the year ended December 31, 2023, G&A expenses were $32.7 million, as compared to $16.4 million for the full year 2022. The increase was primarily due to increases in professional services and employee related expenses as the Company expanded its infrastructure to drive and support the growth in its operations as a publicly-traded company. Net Loss: Net loss for the fourth quarter of 2023 totaled $24.5, with non-cash stock-based compensation expense of $2.1 million, compared to $11.9 million for the fourth quarter of 2022 with non-cash stock-based compensation expense of $0.6 million. For the year ended December 31, 2023, net loss totaled $89.6 million, with non-cash stock-based compensation expense of $8.2 million, compared to $51.3 million for the full year 2022 with non-cash stock-based compensation expense of $2.5 million. About Structure TherapeuticsStructure Therapeutics is a leading clinical-stage biopharmaceutical company focused on discovering and developing innovative oral treatments for chronic metabolic and cardiopulmonary conditions with significant unmet medical needs. Utilizing its next generation structure-based drug discovery platform, the Company has established a scientifically-driven, GPCR-targeted pipeline, featuring two wholly-owned proprietary clinical-stage small molecule compounds designed to surpass the limitations of traditional biologic and peptide therapies and be accessible to more patients around the world. For additional information, please visit www.structuretx.com. Forward Looking Statements This press release contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical fact are statements that could be deemed forward-looking statements, including, without limitation, statements concerning the Company’s future plans and prospects, the Company’s anticipated cash runway, the clinical update from Structure’s Phase 2a study of GSBR-1290 in patients with T2DM and obesity, any expectations regarding the safety, efficacy or tolerability of GSBR-1290 and other candidates under development, the ability of GSBR-1290 to treat T2DM, obesity or related indications, the planned initiation and study design of Structure’s Phase 2b studies for GSBR-1290 in patients with T2DM and obesity and the timing thereof, and first-in-human study of LTSE-2578 and the timing thereof, respectively, the selection of a development candidate for the Company’s amylin receptor agonist program and GLP-1R/GIPR program, the planned timing of the Company’s data results and continued development of GSBR-1290, amylin and next generation GLP-1R/GIPR combination candidates and expectations regarding an oral development candidate targeting GLP-1R. In addition, when or if used in this press release, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to the Company may identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Although the Company believes the expectations reflected in such forward-looking statements are reasonable, the Company can give no assurance that such expectations will prove to be correct. Readers are cautioned that actual results, levels of activity, safety, performance or events and circumstances could differ materially from those expressed or implied in the Company’s forward-looking statements due to a variety of risks and uncertainties, which include, without limitation, risks and uncertainties related to the preliminary nature of the results due to length of the study and sample size, the risks that unblinded data is not consistent with blinded data, the Company’s ability to advance GSBR-1290, LTSE-2578, ANPA-0073 and its other therapeutic candidates, obtain regulatory approval of and ultimately commercialize the Company’s therapeutic candidates, the timing and results of preclinical and clinical trials, the impact of any data collection omissions at any of our clinical sites, the Company’s ability to fund development activities and achieve development goals, the impact of any global pandemics, inflation, supply chain issues, rising interest rates and future bank failures on the Company’s business, its ability to protect its intellectual property and other risks and uncertainties described in the Company’s filings with the Securities and Exchange Commission (SEC), including the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, as filed with the SEC on November 17, 2023, and future reports the Company may file with the SEC from time to time. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. STRUCTURE THERAPEUTICS INC.Condensed Consolidated Statements of Operations(unaudited)(In thousands, except per share amounts) THREE MONTHS ENDED YEAR ENDED DECEMBER 31, DECEMBER 31, 2023 2022 2023 2022Operating expenses: Research and development $20,042 $8,360 $70,103 $36,193 General and administrative 10,952 4,596 32,672 16,368 Total operating expenses 30,994 12,956 102,775 52,561 Loss from operations (30,994) (12,956) (102,775) (52,561)Interest and other income (expense), net 6,179 901 13,391 1,257 Loss before provision for income taxes (24,815) (12,055) (89,384) (51,304)Provision for income taxes (312) (180) 236 17 Net loss $(24,503) $(11,875) $(89,620) $(51,321) STRUCTURE THERAPEUTICS INC.Condensed Consolidated Balance Sheet Data(unaudited)(In thousands) DECEMBER 31, 2023 2022Assets Current assets: Cash, cash equivalents and short-term investments $467,323 $90,841 Prepaid expenses and other current assets 6,285 2,248 Total current assets 473,608 93,089 Property and equipment, net 3,228 1,031 Operating right-of-use assets 5,136 262 Other non-current assets 45 3,463 Total assets $482,017 $97,845 Liabilities, redeemable convertible preferred shares and shareholders’ equity (deficit) Current liabilities: Accounts payable $4,742 $6,009 Accrued expenses and other current liabilities 18,558 6,741 Operating lease liabilities, current portion 1,440 260 Total current liabilities 24,740 13,010 Operating lease liabilities, net of current portion 4,013 — Other non-current liabilities 298 — Total liabilities 29,051 13,010 Redeemable convertible preferred shares issuable in series — 199,975 Total shareholders’ equity (deficit) 452,966 (115,140)Total liabilities, redeemable convertible preferred shares and shareholders’ equity (deficit) $482,017 $97,845 Investors:Danielle KeatleyStructure Therapeutics Inc.ir@structuretx.com Media:Dan Budwick1ABDan@1abmedia.com

US regulators have approved a label expansion for Novo Nordisk's weight-loss drug Wegovy (semaglutide) to reduce the risk of major adverse cardiovascular events (MACE), including heart attacks and strokes. The decision could potentially broaden insurance coverage for the GLP-1 agonist and similar treatments for obesity."We are very pleased that Wegovy is now approved in the US as the first therapy to help people manage their weight and reduce CV risks," said Martin Holst Lange, head of development at Novo Nordisk. The once-weekly injection was first cleared for chronic weight management in adults back in 2021, and later expanded to include children as young as 12 years old.'Major advance' for public healthThe latest approval is based on the Phase III SELECT cardiovascular (CV) outcomes trial, which demonstrated that Wegovy significantly reduced the risk of MACE by 20% compared to placebo when added to standard care.Specifically, the new indication is for reducing risks of MACE including CV death, non-fatal heart attack or non-fatal stroke in overweight or obese adults with established CV disease. The label update also includes data from SELECT showing a risk reduction in CV death by 15% and a risk reduction in death from any cause by 19%, both compared to placebo."Providing a treatment option that is proven to lower this CV risk is a major advance for public health," stated John Sharretts, who directs FDA's division of diabetes, lipid disorders and obesity. Novo Nordisk has also asked EU regulators to expand the use of Wegovy for heart conditions, although they have not yet weighed in on the request.Lifting coverage barrierPrivate insurers will evaluate the new indication for Wegovy before making coverage decisions, said a spokesperson for America's Health Insurance Plans, an industry trade group. At the moment, Medicare is currently legally barred from covering drugs for weight-loss alone, although Novo Nordisk has been trying to make the case that its drug is not just about weight and appearance, but about improving aspects of overall health.Aside from the SELECT trial, the company also recently reported that semaglutide, which is marketed for diabetes as Ozempic, cut the risk of kidney disease progression and death from kidney or CV complications by 24% in certain patients in another Phase III trial.However, besides the issue of insurance coverage, ongoing supply constraints for Wegovy have also been a persistent barrier to broader uptake, although the company is working to ramp up production.Competitor battleThe new label could allow the Danish drugmaker to maintain an edge over Eli Lilly, whose rival weight-loss treatment Zepbound (tirzepatide) was approved in the US last November. Despite the dual GIP and GLP-1 agonist's efficacy in helping people lose weight, it has yet to demonstrate a CV impact – and a readout from the study searching for such a benefit was recently delayed. On its fourth quarter earnings call, Eli Lilly bumped back the timing for the Phase III SURPASS CV outcomes study from the end of 2024 into 2025. For a comprehensive timeline of clinical weight loss programmes, see Vital Signs: Key obesity readouts of 2024.However, a recent physician's poll conducted by FirstWord suggests Zepbound is chomping away at Wegovy's market share. Examining drug switching activity from other treatments to Zepbound, the poll found that the predominant shift has been from Wegovy, as reported by 42% of physicians.  Meanwhile, Novo Nordisk is working on a once-daily oral formulation of semaglutide, and also provided an early glimpse this week of another potential oral weight-loss contender – this time targeting both GLP-1 and amylin. For more, see Spotlight On: Novo Nordisk’s latest obesity outlook - 5 key takeaways.

Pictured: Novo Nordisk's office in Fremont, California/iStock, hapabapa Novo Nordisk during the company’s Capital Markets Day event on Thursday unveiled positive Phase I data for its next-generation obesity therapy amycretin, demonstrating an overall favorable safety pro strong weight-loss signals. At 12 weeks, study participants who were given the investigational drug saw a 13.1% weight loss, the Danish pharma reported in its R&D presentation at the investor event. The placebo group, on the other hand, saw only a 1.1% reduction in body weight over the same time span. Amycretin was also safe and well-tolerated overall and its adverse effects were in line with Novo’s prior studies of GLP-1 receptor agonists, the company said. The pharmacokinetic findings in the Phase I study also encourage further assessment of amycretin. Designed to be orally available, amycretin is a co-agonist of both the GLP-1 and amylin receptors—both of which are involved in regulating appetite and controlling blood glucose levels, though their effects are mediated through complementary pathways. Amylin receptors are located on β-cells in the pancreas, while GLP-1 receptors are concentrated in L-cells in the intestine. According to Novo’s presentation, amycretin is a unimolecular candidate, meaning that it combines two mechanisms of action in a single molecule and yields additive effects. Novo is developing amycretin as part of its pipeline in diabetes and obesity, which seeks to maximize its current GLP-1 franchise and leverage other innovative approaches including those that target amylin and GIP receptors. For future projects, Novo will focus on regulating appetite and energy expenditure, maintaining weight, preserving lean mass and evaluating sustained-release modes of delivery. The pharma is looking to start another amylin program in the coming months, with a Phase I trial slated for 2024. Novo is also gearing up for another Phase I study in the next 12 months for a new tri-agonist candidate, which the company contends has the potential for greater weight loss and other obesity-related comorbidities. Aside from amycretin and the upcoming Phase I programs, Novo is already targeting the amylin pathway through its late-stage weight-loss combo therapy CagriSema, which combines the top-selling semaglutide—marketed as Ozempic for type 2 diabetes and Wegovy for chronic weight management—with an amylin analog dubbed cagrilintide. In August 2022, the drugmaker released Phase II data for CagriSema, demonstrating a 15.6% drop in body weight in type 2 diabetes patients who were overweight. This effect was numerically better when compared with cagrilintide or Wegovy alone. In September 2023, Novo launched a Phase III head-to-head trial pitting CagriSema against Eli Lilly’s Zepbound (tirzepatide). Novo is also seeking to expand its expertise beyond obesity and diabetes, targeting cardiometabolic diseases more broadly. On Tuesday, the pharma reported that Ozempic induced a 24% reduction in the risk of kidney disease progression, major adverse cardiovascular events and kidney death versus placebo in patients with type 2 diabetes and chronic kidney disease. Novo is eyeing a label expansion for Ozempic, with filings planned for later this year. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.