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Subset analysis of FASCINATE-2 Phase 2 trial demonstrated denifanstat improved fibrosis in difficult-to-treat MASH patients Both artificial intelligence (AI) and conventional pathology demonstrated denifanstat's strong anti-fibrotic activity FASN inhibitor treatment reduced atherosclerosis development in mouse model of dyslipidemia and MASH SAN MATEO, Calif., Nov. 18, 2024 (GLOBE NEWSWIRE) -- Sagimet Biosciences Inc. (Sagimet, Nasdaq: SGMT), a clinical-stage biopharmaceutical company developing novel therapeutics targeting dysfunctional metabolic and fibrotic pathways, today announced the presentation of Phase 2b data demonstrating the anti-fibrotic activity of its fatty acid synthase (FASN) inhibitor denifanstat, and preclinical data demonstrating potential benefit of FASN inhibition in atherosclerosis, at the American Association for the Study of Liver Disease (AASLD) - The Liver Meeting 2024®, November 15-19, 2024 in San Diego, California. “Our presentations of data from the Phase 2b FASCINATE-2 study highlight denifanstat’s impact on liver fibrosis, particularly in difficult-to-treat subsets of MASH patients who are at the highest risk of disease progression,” said Dave Happel, Chief Executive Officer of Sagimet. “Using an AI-based digital pathology approach, we observed pronounced fibrosis reduction in the peri-portal and portal zones of the liver, which as part of composite scores have recently been shown to correlate with liver outcomes and mortality, that may not be captured using conventional histological scoring. Finally, our preclinical data in a mouse model of MASH and dyslipidemia treated with a FASN inhibitor that is a surrogate for denifanstat showed that a FASN inhibitor may reduce circulating cholesterol and atherosclerosis development. Together, these results demonstrate the anti-fibrotic effects and potential cardiometabolic benefits of FASN inhibition and support the advancement of denifanstat into Phase 3 development.” A poster titled “Denifanstat significantly improves liver fibrosis in difficult-to-treat MASH patients – Results from conventional and AI-based pathology from the phase 2b FASCINATE-2, a 52-week randomized, double-blind, placebo-controlled trial,” was presented by 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, the primary investigator of the FASCINATE-2 trial. Denifanstat treatment improved fibrosis by ≥ 1 stage without worsening of MASH in the higher-risk patient subgroups described below. Observed improvements by conventional pathology reading included: F3 population: 49% denifanstat (n=47) vs 13% placebo (n=23) (p=0.0032)GLP1 receptor agonist population: 42% denifanstat (n=12) vs 0% placebo (n=4) (p=0.034)Type 2 diabetes population: 40% denifanstat (n=55) vs 19% placebo (n=27) (p=0.0382)PNPLA3 I148 carrier population: 30% denifanstat (n=33) vs 6% placebo (n=17) (p=0.022) Strong consistency in fibrosis improvement was observed between conventional and AI-based pathology in the F3 population. Denifanstat treatment improved fibrosis by ≥ 1 stage in more than 50% of F3 patients as follows: AI-based: 62% denifanstat (n=47) and 26% placebo (n=23) (p=0.005)Conventional: 55% denifanstat (n=47) and 26% placebo (n=23) (p=0.021) An oral presentation titled “AI-based digital pathology shows that denifanstat improves multiple parameters of fibrosis and reduces progression to cirrhosis in MASH patients with F2/F3 fibrosis – results of the FASCINATE-2 study,” was presented by Mary Rinella, M.D. (University of Chicago). In this analysis, second harmonic generation (SHG) microscopy AI-based digital pathology was used to evaluate pre- and post-treatment liver biopsies. Denifanstat showed statistically significant liver fibrosis improvement, particularly in the portal and peri-portal regions. Improvement was observed with AI-based digital pathology not only in patients with >1-stage fibrosis improvement but also in patients with “no change” in fibrosis stage by conventional reading, representing important mechanistic insights provided by the AI-based platform. Select fibrosis parameters in the periportal and portal regions are part of AI-based composite score that have been recently linked to liver outcomes and mortality. Overall, both AI and conventional pathology readings demonstrated denifanstat's strong anti-fibrotic activity in MASH patients, including those with high risk of progression. These data reflect the unique mechanism of action of denifanstat and support the initiation of phase 3 trials. Lastly, a poster titled “Fatty acid synthase (FASN) inhibitor reduces atherosclerosis development in diet-induced dyslipidaemia LDL receptor knockout mice with MASH,” was presented by Wen-Wei Tsai, Ph.D. (Sagimet Biosciences). In this mouse model, treatment with a FASN inhibitor that is a preclinical surrogate for denifanstat rapidly reduced circulating cholesterol, triglycerides and inflammatory markers associated with atherosclerosis, including CCL4 and CXCL2. The FASN inhibitor also reduced total atherosclerotic lesion area in the aortic root and improved liver steatosis, inflammation and fibrosis. These preclinical results suggest that a FASN inhibitor such as denifanstat could potentially provide benefits in cardiovascular as well as liver health, supporting the clinical evaluation of denifanstat for long term outcomes in MASH patients. About Sagimet Biosciences Sagimet is a clinical-stage biopharmaceutical company developing novel fatty acid synthase (FASN) inhibitors that are designed to target dysfunctional metabolic and fibrotic 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 metabolic dysfunction associated steatohepatitis (MASH). FASCINATE-2, a Phase 2b clinical trial of denifanstat in MASH with liver biopsy-based primary endpoints, was successfully completed with positive results. Denifanstat has been granted Breakthrough Therapy designation by the FDA for the treatment of non-cirrhotic MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), and end-of-Phase 2 interactions with the FDA have been successfully completed, supporting the advancement of denifanstat into Phase 3 development in MASH. For additional information about Sagimet, please visit www.sagimet.com. About MASH Metabolic dysfunction associated steatohepatitis (MASH) 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 to improve diagnostic clarity. Forward-Looking Statements This 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

Cleared First Four Monotherapy Doses and Initial Combination Cohort with No Dose Limiting Toxicities at any Dose Level KVA12123 Monotherapy Demonstrated Dose Proportional Induction of Pro-inflammatory Biomarkers Required for Strong Anti-tumor Activity Additional Monotherapy Clinical Efficacy Data and Initial Combination Clinical Data Anticipated in Q2 2024 Jan. 17, 2024 -- Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, announced today an update on its ongoing VISTA-101 Phase 1/2 clinical trial evaluating KVA12123 in patients with advanced solid tumors. KVA12123, Kineta’s novel VISTA blocking immunotherapy, cleared the first four monotherapy dose levels and the first cohort in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab). KVA12123 was well tolerated with no dose limiting toxicities (DLT) or cytokine related adverse events at any dose level. Additionally, KVA12123 demonstrates robust and dose proportional induction of pro-inflammatory biomarkers required for strong anti-tumor activity, demonstrating on target effects of blocking VISTA. “We are encouraged with the efficacy-related biomarker data that demonstrate on-target activity of KVA12123 in our Phase 1/2 clinical trial. Additionally, the safety profile supports advancing to higher doses in the monotherapy and combination cohorts of the study,” said Shawn Iadonato, Ph.D., Chief Executive Officer of Kineta. “We believe KVA12123 continues to show its potential as a next-generation immunotherapy that may overcome immunosuppression in the tumor microenvironment. The clinical study is progressing on time, and we anticipate fully enrolling the Phase 1 portion of the trial by April 2024.” In the VISTA-101 trial (NCT05708950), a total of 18 patients have been dosed with KVA12123. 15 patients with advanced solid tumors were enrolled in the first four monotherapy dose-escalation cohorts, where subjects received either 3, 10, 30 or 100 mg of KVA12123 by intravenous (IV) infusion every two weeks. Additionally, 3 patients were enrolled in the initial combination cohort with 30 mg KVA12123 and 400mg of pembrolizumab. Primary objectives of the Phase 1/2 study are to evaluate the safety and tolerability of KVA12123 and to determine the recommended Phase 2 dose (RP2D). Patients enrolled in the study were heavily pretreated with multiple prior lines of therapy including chemotherapy, radiation, and immunotherapy. Approximately half of the enrolled patients failed prior checkpoint inhibitor therapy. Dosing of the 300 mg monotherapy and 100 mg in combination with pembrolizumab cohorts have been initiated. In the first four monotherapy cohorts and initial cohort in combination with pembrolizumab, KVA12123 was well tolerated at all doses and no DLTs were observed. During Phase 1, the study is closely monitoring the proinflammatory IL-6 and TNFα cytokines that are associated with cytokine release syndrome (CRS). No evidence of CRS-associated cytokine induction has been observed at any dose level with KVA12123 in the initial cohorts. KVA12123 demonstrated dose proportional induction of pro-inflammatory biomarkers including CXCL10, CCL2, CCL3 and CCL4 that are required for strong anti-tumor activity. Consistent increases in anti-tumor non-classical monocytes, NK cells, helper (CD4+) and cytotoxic (CD8+) T cells in the blood were also observed. These key pro-inflammatory myeloid derived cytokines and chemokines are involved in immune cell activation and recruitment in the tumor microenvironment (TME). To guide the recommended Phase 2 dose (RP2D) decision, Kineta developed a proprietary assay to evaluate VISTA RO on immune cells from patients in the clinical trial. KVA12123 achieved a greater than 90% VISTA RO at the 30 and 100 mg doses. Furthermore, pharmacokinetic analyses demonstrated a greater than dose-proportional increase in drug exposure across all evaluated doses, consistent with target-mediated drug disposition at lower doses. “We are pleased to see the compelling safety data of KVA12123 and lack of CRS-associated cytokine induction. The drug has been very well tolerated in patients,” said Thierry Guillaudeux, Ph.D., Chief Scientific Officer of Kineta. “These data are encouraging and consistent with the results from our preclinical models.” Kineta (Nasdaq: KA) is a clinical-stage biotechnology company with a mission to develop next-generation immunotherapies that transform patients’ lives. Kineta has leveraged its expertise in innate immunity and is focused on discovering and developing potentially differentiated immunotherapies that address the major challenges with current cancer therapy. The company’s immuno-oncology pipeline includes KVA12123, a novel VISTA blocking immunotherapy currently in a Phase 1/2 clinical trial in patients with advanced solid tumors, and a preclinical monoclonal antibody targeting CD27. For more information on Kineta, please visit www.kinetabio.com, and follow Kineta on Twitter, LinkedIn and Facebook. KVA12123 is a VISTA blocking immunotherapy in development as a twice weekly monoclonal antibody infusion drug being evaluated in a Phase 1/2 clinical trial for patients with advanced solid tumors. Competitive therapies targeting VISTA have demonstrated either poor monotherapy anti-tumor activity in preclinical models or induction of cytokine release syndrome (CRS) in human clinical trials. Through the combination of unique epitope binding and an optimized IgG1 Fc region, KVA12123 demonstrates strong monotherapy tumor growth inhibition in preclinical models without evidence of CRS in clinical trial participants. KVA12123 has been shown to de-risk the VISTA target and provides a novel approach to address immune suppression in the TME with a mechanism of action that is differentiated and complementary with T cell focused therapies. KVA12123 may be an effective immunotherapy for many types of cancer including non-small cell lung (NSCLC), colorectal, renal cell carcinoma, head and neck, and ovarian cancer. VISTA (V-domain Ig suppressor of T cell activation) is a negative immune checkpoint that suppresses T cell function in a variety of solid tumors. High VISTA expression in tumor correlates with poor survival in cancer patients and has been associated with a lack of response to other immune checkpoint inhibitors. Blocking VISTA induces an efficient polyfunctional immune response to address immunosuppression and drives anti-tumor responses. The content above comes from the network. if any infringement, please contact us to modify.

TAIPEI and SAN DIEGO, Dec. 26, 2023 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), a drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, announced today that Taiwan Food and Drug Administration has approved its Phase II IND application of Silmitasertib (CX-4945) to treat patients with community-acquired pneumonia (CAP) caused by viral infection. The trial is a phase II multi-center, randomized-controlled interventional prospective study, and the purpose of this trial is to investigate whether early intervention of Silmitasertib restrains the progression of CAP by inhibiting the elevated cytokine release associated with SARS-CoV-2 and Influenza viruses. This trial will be led by an inter-hospital team, which is specialized in infectious diseases and possesses extensive experiences in carrying out large-scale international clinical trials for various anti-viral new drugs, across five well-known hospitals including National Taiwan University Hospital, National Taiwan University Cancer Center, Far Eastern Memorial Hospital, Tri-Service General Hospital and Taoyuan General Hospital, Ministry of Health and Welfare. Silmitasertib works by inhibiting CK2 protein kinase, which have implicated in regulation of several signaling pathways that are important for innate immune responses. CK2 modulates inflammatory pathways, including NF-κB, PI3K–Akt–mTOR, and JAK–STAT. Inhibition of CK2 by Silmitasertib diminishes the secretion of IL-6 and MCP-1 (Rosenberger et al.). Silmitasertib treatment also reduces the expression of TNF-α and CCL4 in NiSO4-stimulated MoDCs (Bourayne et al.). "Senhwa regards this phase II as the proof-of-concept study to demonstrate Silmitasertib can be a therapeutic strategy that are not restricted to only a specific viral infection, but applicable to various viruses," said Jin-Ding Huang, CEO of Senhwa Biosciences, Inc. The global market for related therapeutic drugs has exceeded a value of over $120.6 billion USD in 2020 and it's projected to grow at a CAGR of 7.88% and reach more than $339 billion USD by 2030 according to market research. About Silmitasertib Silmitasertib is a first-in-class small molecule drug that targets the CK2 protein and acts as a CK2 inhibitor. Clinical studies thus far have shown Silmitasertib is safe and well-tolerated in humans and is easily administered with its oral formulation. Silmitasertib is currently under development through several oncology programs in adults and children with recurrent/advanced or metastatic cancer. To date, three Phase I trials and one Phase II trial of Silmitasertib in cancer patients have been completed while two other Phase I and II studies of Silmitasertib are still ongoing. The US FDA has granted Silmitasertib Orphan Drug Designation for the treatment of Cholangiocarcinoma in December 2016, Rare Pediatric Disease Designation and Orphan Drug Designation for the treatment of Medulloblastoma in July 2020 and December 2021, respectively. Fast Track Designation was granted in August 2021 for the treatment of recurrent Sonic Hedgehog driven Medulloblastoma. About Senhwa Biosciences Senhwa Biosciences, Inc. is a leading clinical-stage company focused on developing first-in-class, next-generation DNA Damage Response therapeutics and seeks to address unmet medical needs in oncology and infectious diseases. Headquartered in Taiwan, with an operational base in San Diego, California, Senhwa is well-positioned to oversee the development of its compounds. Silmitasertib (CX-4945) and Pidnarulex (CX-5461), both with novel mechanisms of action as anti-cancer drugs for the treatment of multiple indications, are the core products in Senhwa Bioscience's pipeline. Clinical trials are currently ongoing in Australia, Canada, United States and Taiwan. Visit Senhwa Biosciences' website for more details: SOURCE Senhwa Biosciences, Inc.