BEBT-808

LONDON — After a recent spate of setbacks, Novo Nordisk has raised the curtain on data detailing semaglutide’s ability to cut the risk of heart failure and cardiovascular death in a late-phase test of type 2 diabetes patients with chronic kidney disease. The results are important because Novo plans to resubmit the GLP-1 agonist for heart failure patients with obesity with these additional results from the Phase 3 FLOW trial, after it yanked its original FDA filing earlier this month. The resubmission is part of Novo’s efforts to expand semaglutide’s use beyond diabetes and obesity with an eye to broader reimbursement . The company has already secured an FDA thumbs up for Wegovy — the version of the semaglutide used for weight loss — to reduce the risk of major adverse cardiovascular events in overweight or obese adults with established cardiovascular disease. In the placebo-controlled FLOW study, patients given semaglutide saw a 27% relative risk reduction in composite heart failure events or cardiovascular death at median follow-up of around 40 months (p=0.0005), according to the results of a prespecified analysis presented to a packed room Friday at the European Society of Cardiology annual meeting in London. When the endpoint was split into separate parts, the patients saw a 27% relative risk reduction in heart failure events and a 29% relative risk reduction in cardiovascular events. “The data itself is kind of resounding,” Ali Pashazadeh, founder of strategic advisory firm Treehill Partners, told Endpoints News in an interview, adding they would likely support approval and adoption of the drug. But Pashazadeh also said that the thought of using GLP-1s for many years — which is typical of heart medications — raises concerns because “that’s not what GLP-1s were designed to do.” He said he would like to see more data on the long-term safety profile of the drug class. The FLOW trial set 1 mg semaglutide against placebo as an adjunct to standard of care in more than 3,500 people with type 2 diabetes and chronic kidney disease. Topline data released in March showed the drug cut the risk of kidney disease progression and cardiovascular and kidney death by almost a quarter compared with placebo in the trial’s primary endpoint. In May, Novo reported success in key secondary endpoints , with semaglutide slashing the risk of major cardiovascular events by 18% and all-cause mortality by 20%. Results from a separate semaglutide trial in adults with heart failure with preserved ejection fraction and obesity — called STEP HFpEF — formed the basis of an FDA filing for a label expansion for this population. But in August, Novo disclosed it had pulled its filing in a surprise move after discussions with the FDA, and said it will resubmit the application next year with more data, including from FLOW. Just a few days before that, Eli Lilly reported that its GLP-1 tirzepatide slashed the risk of a heart failure urgent visit or hospitalization, oral diuretic intensification or cardiovascular death by 38% versus placebo in a Phase 3 trial in the same indication as STEP HFpEF. Pashazadeh said it’s difficult to compare results between the Novo and Lilly studies because of slightly different patient characteristics, adding “it remains to be seen” which GLP-1 is more effective in terms of heart outcomes. “I do think we’re going to see slightly different efficacy between the GLP-1s in different contexts,” he added. Novo has faced a number of challenges in recent months, including its second-quarter sales falling short of Wall Street expectations. Even so, in the US alone, its GLP-1 franchise pulled in 46 billion DKK ($6.7 billion) for diabetes for the first half of the year. In July, the drugmaker also lost its case against the Inflation Reduction Act, although the company said it plans to appeal the decision. That same month, the FDA rejected Novo’s once-weekly insulin formulation, insulin icodec, because it had remaining questions about the manufacturing process for the treatment. The drugmaker said it doesn’t expect to be able to meet the regulator’s requests this year. Eli Lilly, meanwhile, upped its 2024 revenue guidance on the back of the strong performance of its GLP-1 franchise.

Denifanstat Phase 2b FASCINATE-2 clinical trial 52-week data was presented in June at the European Association for the Study of the Liver (EASL) Congress Preparations are ongoing to initiate a Phase 3 clinical development program for denifanstat in patients with metabolic dysfunction-associated steatohepatitis (MASH) in the second half of 2024 Two biotechnology industry leaders, Anne Phillips and Jennifer Jarrett, joined the Board of Directors effective August 1, 2024 Anticipated cash runway through 2025 with cash, cash equivalents and marketable securities totaling $188.5 million as of June 30, 2024 SAN MATEO, Calif., Aug. 14, 2024 (GLOBE NEWSWIRE) -- Sagimet Biosciences Inc. (Nasdaq: SGMT), a clinical-stage biopharmaceutical company developing novel therapeutics targeting dysfunctional metabolic pathways, today reported financial results for the second quarter ended June 30, 2024, and provided recent corporate updates. “In June, we presented the full Phase 2b FASCINATE-2 clinical trial 52-week biopsy results at EASL showing denifanstat’s statistically significant fibrosis reduction in advanced F2 and F3 patients and a statistically significant delay in progression to cirrhosis,” said David Happel, Chief Executive Officer of Sagimet. “We believe these encouraging data, which demonstrate denifanstat’s mechanism of action as the only fat synthesis inhibitor that directly targets the three key drivers of MASH -- fat accumulation, inflammation, and fibrosis -- differentiate denifanstat from other therapeutics in the field. We plan to initiate the Phase 3 program for denifanstat in MASH in the second half of 2024 and intend to share the Phase 3 pivotal trial design later in the year. We look forward to progressing the development of denifanstat for patients living with MASH, a condition which has grown to epidemic levels worldwide.” Recent Corporate Highlights On June 6, 2024, Sagimet presented the full 52-week data from the ITT and F3 patient population in the Phase 2b FASCINATE-2 clinical trial of denifanstat at EASL. Key outcomes data included: A statistically significant improvement in liver fibrosis by ≥1-stage without worsening of MASH at 52-weeks in ITT population and in patients with baseline stage 3 fibrosis. ITT (denifanstat 30% vs. placebo 14%, p=0.0199), andF3 mITT (denifanstat 49% vs. placebo 13%, p=0.0032) A statistically significant improvement in liver fibrosis by ≥2-stage without worsening of MASH at 52-weeks in mITT population and in patients with baseline stage 3 fibrosis. mITT (denifanstat 20% vs. placebo 2%, p=0.0065), andF3 mITT (denifanstat 34% vs. placebo 4%, p=0.0065) A statistically significant difference in progression to cirrhosis in F4 mITT population (denifanstat 5% vs. placebo 11%, p=0.0386).A statistically significant difference in fibrosis improvement by ≥ 1 stage with no worsening of MASH for patients on a stable background dose of a GLP-1RA (denifanstat 42% vs. placebo 0%, p=0.034) in mITT population.A statistically significant increase in beneficial polyunsaturated triglycerides at the end of 52 weeks of treatment (+42% denifanstat vs. -4% placebo, p<0.001) in the mITT population.Tripalmitin, a biomarker of denifanstat activity, showed an early and sustained reduction in de novo lipogenesis at 4-weeks (-2.4ug/ml with denifanstat vs. -0.4ug/mL placebo, p=0.001) and 13-weeks (-2.2ug/mL with denifanstat vs. -0.1ug/mL placebo, p=0.005) in the ITT population. On June 13, the Company hosted a conference call and webcast (link here) featuring Rohit Loomba, M.D., M.H.Sc., Professor of Medicine, Chief, Division of Gastroenterology and Hepatology, and Director, MASLD Research Center, University of California San Diego, and Principal Investigator of the Phase 2b FASCINATE-2 clinical trial. In the webcast, Dr. Loomba reviewed denifanstat’s strong fibrosis data as well as the preclinical data supporting the potential clinical use of denifanstat in combination with other medicines such as GLP-1s and thyroid-hormone receptor-beta (TRβ) agonists, including resmetirom, which he indicated could synergistically improve outcome of disease.On August 1, the Company announced the appointment to its board of directors of Dr. Anne Phillips and Jennifer Jarrett, two biotechnology industry leaders with extensive experience in clinical development, regulatory strategy, operations, and finance. Anticipated Upcoming Milestones Following the company’s End-of-Phase 2 meeting with the FDA in May 2024, discussions are currently ongoing with the FDA regarding the Phase 3 development plans for denifanstat in MASH. A contract with a Contract Research Organization (CRO) for the global Phase 3 development program has been executed and study start-up operational activities are ongoing. Pending the FDA’s feedback, the company plans to start the Phase 3 program in the second half of 2024.The Phase 3 study of denifanstat in acne, conducted by license partner Ascletis Pharmaceuticals, is recruiting in China and expected to be fully enrolled by the end of 2024. This Phase 3 study was initiated after positive Phase 2 acne data reported in Q2 2023 [link]. Financial Results for the Three and Six Months Ended June 30, 2024 Cash and cash equivalents and marketable securities as of June 30, 2024 was $188.5 million, including $104.7 million net proceeds from our January 2024 follow-on offering, which are expected to fund operations through 2025 based on management’s current operating plan. Research and development expense for the three and six months ended June 30, 2024 was $6.3 million and $11.6 million, respectively, compared to $4.7 million and $9.2 million for the three and six months ended June 30, 2023, respectively.General and administrative expense for the three and six months ended June 30, 2024 was $4.3 million and $7.8 million, respectively, compared to $2.4 million and $4.7 million for the three and six months ended June 30, 2023, respectively.Net loss for the three and six months ended June 30, 2024 was $8.1 million and $14.7 million, respectively, compared to $6.8 million and $13.4 million for the three and six months ended June 30, 2023, respectively. About Sagimet Biosciences Sagimet is a clinical-stage biopharmaceutical company developing novel fatty acid synthase (FASN) inhibitors that are designed to target dysfunctional metabolic pathways in diseases resulting from the overproduction of the fatty acid, palmitate. Sagimet’s lead drug candidate, denifanstat, is an oral, once-daily pill and selective FASN inhibitor in development for the treatment of MASH. FASCINATE-2, a Phase 2b clinical trial of denifanstat in MASH with liver biopsy-based primary endpoints, was successfully completed with positive results. For additional information about Sagimet, please visit www.sagimet.com. About MASHMASH is a progressive and severe liver disease which is estimated to impact more than 115 million people worldwide, for which there is only one recently approved treatment in the United States and no currently approved treatments in Europe. In 2023, global liver disease medical societies and patient groups formalized the decision to rename non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) and nonalcoholic steatohepatitis (NASH) to MASH. Additionally, an overarching term, steatotic liver disease (SLD), was established to capture multiple types of liver diseases associated with fat buildup in the liver. The goal of the name change was to establish an affirmative, non-stigmatizing name and diagnosis. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, The Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements regarding: the expected timing of the presentation of data from ongoing clinical trials, Sagimet’s clinical development plans and related anticipated development milestones, Sagimet’s cash and financial resources and expected cash runway. These statements involve known and unknown risks, uncertainties and other important factors that may cause Sagimet’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, these statements can be identified by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this press release are only predictions. Sagimet has based these forward-looking statements largely on its current expectations and projections about future events and financial trends that Sagimet believes may affect its business, financial condition and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond Sagimet’s control, including, among others: the clinical development and therapeutic potential of denifanstat or any other drug candidates Sagimet may develop; Sagimet’s ability to advance drug candidates into and successfully complete clinical trials within anticipated timelines, including its Phase 3 denifanstat program; Sagimet’s relationship with Ascletis, and the success of its development efforts for denifanstat; the accuracy of Sagimet’s estimates regarding its capital requirements; and Sagimet’s ability to maintain and successfully enforce adequate intellectual property protection. These and other risks and uncertainties are described more fully in the “Risk Factors” section of Sagimet’s most recent filings with the Securities and Exchange Commission and available at www.sec.gov. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in these forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, Sagimet operates in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that Sagimet may face. Except as required by applicable law, Sagimet does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contact:Joyce Allaire LifeSci Advisors JAllaire@LifeSciAdvisors.com SAGIMET BIOSCIENCES INC.CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS(Unaudited)(in thousands, except for share and per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Operating expenses: Research and development $6,313 $4,676 $11,575 $9,163 General and administrative 4,276 2,381 7,782 4,659 Total operating expenses 10,589 7,057 19,357 13,822 Loss from operations (10,589) (7,057) (19,357) (13,822) Interest income and other 2,471 272 4,610 450 Net loss $(8,118) $(6,785) $(14,747) $(13,372) Other comprehensive income (loss): Net unrealized income (loss) on marketable securities (30) 13 (53) 84 Comprehensive loss $(8,148) $(6,772) $(14,800) $(13,288) Net loss per share, basic and diluted $(0.25) $(35.80) $(0.48) $(71.39) Weighted-average shares outstanding, basic and diluted 31,913,887 189,520 30,476,657 187,314 SAGIMET BIOSCIENCES INC. CONDENSED BALANCE SHEETS(Unaudited)(in thousands) As of June 30, 2024 December 31, 2023 Cash, cash equivalents and marketable securities $188,491 $94,897 Total assets $189,020 $96,719 Current liabilties $5,728 $5,654 Stockholders' equity $183,292 $91,065 Liabilities and stockholders' equity $189,020 $96,719