This Phase 2a study is designed to evaluate the safety, tolerability, effectiveness, and pharmacokinetics (PK) of TLC-3595 in subjects with insulin resistance.

Start Date08 Mar 2023

Sponsor / Collaborator

Orsobio, Inc.Startup

JPRN-jRCT2051200126 / CompletedPhase 1IIT

A Phase 1, Randomized, Double-Blind, Single-Ascending-Dose, and Food Effect Study to Assess the Safety, Tolerability, and Pharmacokinetics of S-723595 in Healthy Adult Participants (Part 1); and A Phase 1, Randomized, Double-Blind, Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of S-723595 and A Drug-Drug Interaction Study with the CYP3A Substrate, Midazolam, in Healthy Adult Participants (Part 2) - A Phase 1, Single-Dose, Multiple-Dose, Food Effect, and Midazolam Drug-Drug Interaction Study of S-723595

Start Date18 Jan 2021

Sponsor / Collaborator-

100 Clinical Results associated with S-723595

100 Translational Medicine associated with S-723595

100 Patents (Medical) associated with S-723595

Literatures (Medical) associated with S-723595

29 May 2024·JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

Differential Resistance to Acetyl-CoA Carboxylase Inhibitors in Rice: Insights from Two Distinct Target-Site Mutations

Article

Author: Yang, Xia ; Yang, Yuwen ; Liu, Qing ; Guo, Dongshu ; Li, Yongfeng ; Zhou, Zhenzhen ; Hao, Tingting ; Qiu, Zeyu ; Zhang, Baolong ; Hou, Xiaodong ; Ling, Xitie ; Wang, Jinyan ; Jiang, Qun

Weeds present a significant challenge to agricultural productivity, and acetyl-CoA carboxylase (ACCase)-inhibiting herbicides have proven to be effective in managing weed populations in rice fields. To develop ACCase-inhibiting herbicide-resistant rice, we generated mutants of rice ACCase (OsACC) featuring Ile-1792-Leu or Gly-2107-Ser substitutions through ethyl methyl sulfonate (EMS) mutagenesis. The Ile-1792-Leu mutant displayed cross-resistance to aryloxyphenoxypropionate (APP) and phenylpyrazoline (DEN) herbicides, whereas the Gly-2107-Ser mutants primarily exhibited cross-resistance to APP herbicides with diminished resistance to the DEN herbicide. In vitro assays of the OsACC activity revealed an increase in resistance to haloxyfop and quizalofop, ranging from 4.84- to 29-fold in the mutants compared to that in wild-type. Structural modeling revealed that both mutations likely reduce the binding affinity between OsACC and ACCase inhibitors, thereby imparting resistance. This study offers insights into two target-site mutations, contributing to the breeding of herbicide-resistant rice and presenting alternative weed management strategies in rice cultivation.

01 Feb 2024·Clinical and translational science

Investigation of pharmacokinetic drug interaction between clesacostat and DGAT2 inhibitor ervogastat in healthy adult participants

Article

Author: Calle, Roberto A ; Tripathy, Sakambari ; Sawant-Basak, Aarti ; Mendes da Costa, Laure ; Esler, William P ; Bergman, Arthur J ; Gosset, James R ; Mancuso, Jessica

Abstract:

Co‐administration of clesacostat (acetyl‐CoA carboxylase inhibitor, PF‐05221304) and ervogastat (diacylglycerol O‐acyltransferase inhibitor, PF‐06865571) in laboratory models improved non‐alcoholic fatty liver disease (NAFLD)/non‐alcoholic steatohepatitis (NASH) end points and mitigated clesacostat‐induced elevations in circulating triglycerides. Clesacostat is cleared via organic anion‐transporting polypeptide‐mediated hepatic uptake and cytochrome P450 family 3A (CYP3A); in vitro clesacostat is identified as a potential CYP3A time‐dependent inactivator. In vitro ervogastat is identified as a substrate and potential inducer of CYP3A. Prior to longer‐term efficacy trials in participants with NAFLD, safety and pharmacokinetics (PK) were evaluated in a phase I, non‐randomized, open‐label, fixed‐sequence trial in healthy participants. In Cohort 1, participants (n = 7) received clesacostat 15 mg twice daily (b.i.d.) alone (Days 1–7) and co‐administered with ervogastat 300 mg b.i.d. (Days 8–14). Mean systemic clesacostat exposures, when co‐administered with ervogastat, decreased by 12% and 19%, based on maximum plasma drug concentration and area under the plasma drug concentration–time curve during the dosing interval, respectively. In Cohort 2, participants (n = 9) received ervogastat 300 mg b.i.d. alone (Days 1–7) and co‐administered with clesacostat 15 mg b.i.d. (Days 8–14). There were no meaningful differences in systemic ervogastat exposures when administered alone or with clesacostat. Clesacostat 15 mg b.i.d. and ervogastat 300 mg b.i.d. co‐administration was overall safe and well tolerated in healthy participants. Cumulative safety and no clinically meaningful PK drug interactions observed in this study supported co‐administration of these two novel agents in additional studies exploring efficacy and safety in the management of NAFLD.

10 Jan 2024·Antimicrobial agents and chemotherapy

Repurposing a human acetyl-CoA carboxylase inhibitor firsocostat to treat fungal candidiasis alone and in combination

Article

Author: Zeng, Liping ; Xu, Jingchen ; Feng, Ganzhu ; Luo, Peipei ; Yao, Jing ; Hang, Xudong ; Liu, Genyan ; Chen, Tianyu ; Quan, Keao ; Bi, Hongkai ; Tong, Qian

ABSTRACT:

Opportunistic fungal infections, particularly caused by Candida albicans , remain a common cause of high morbidity and mortality in immunocompromised patients. The escalating prevalence of antifungal drug resistance necessitates the immediate exploration of alternative treatment strategies to combat these life-threatening fungal diseases. In this study, we investigated the antifungal efficacy of firsocostat, a human acetyl-CoA carboxylase (ACC) inhibitor, against C. albicans . Firsocostat alone displayed moderate antifungal activity, while combining it with voriconazole, itraconazole, or amphotericin B exhibited synergistic effects across almost all drug-sensitive and drug-resistant C. albicans strains tested. These observed synergies were further validated in two mouse models of oropharyngeal and systemic candidiasis, where the combination therapies demonstrated superior fungicidal effects compared to monotherapy. Moreover, firsocostat was shown to directly bind to C. albicans ACC and inhibit its enzymatic activity. Sequencing spontaneous firsocostat-resistant mutants revealed mutations mapping to C. albicans ACC, confirming that firsocostat has retained its target in C. albicans . Overall, our findings suggest that repurposing firsocostat, either alone or in combination with other antifungal agents, holds promising potential in the development of antifungal drugs and the treatment of candidiasis.

News (Medical) associated with S-723595

18 Sep 2024

·www.globenewswire.com

Standard BioTools proteomics profiling reveals unique biomarkers and insights into nonalcoholic steatohepatitis (NASH)

Researchers used Standard BioTools’ high-content SomaScan® Platform and SomaSignal™ tests for MASH/NASH to identify 69 blood biomarkers that correlate with clinical measures of liver diseaseSOUTH SAN FRANCISCO, Calif., Sept. 18, 2024 (GLOBE NEWSWIRE) -- Standard BioTools Inc. (Nasdaq:LAB) today announced a recent paper published in Nature Scientific Reports, by researchers at Pfizer Research and Development, that detailed their use of the high-plex SomaScan® Assay, leveraging an industry-leading 7,000-protein biomarker panel to analyze blood serum samples from patients in a Phase 2a clinical trial for nonalcoholic fatty liver disease (NAFLD) and NASH. Nonalcoholic Fatty Liver Disease, or NAFLD, and nonalcoholic steatohepatitis (NASH) are becoming a global population health concern. Because diagnosing these diseases involves invasive liver biopsies, which can be challenging and expensive, many patients go untested and untreated. These diseases are complex in their impact on the liver, creating lipid accumulations, stiffness in the liver tissue, ballooning of the liver and chronic inflammation. In collaboration with major pharmaceutical companies and leading academic centers, SomaLogic (now Standard BioTools) previously developed serum proteomic SomaSignal™ tests which correlate more faithfully with each component of the liver biopsy than any other noninvasive biomarkers. Because these tests run on the full SomaScan® Platform, covering thousands of protein measurements, the study’s researchers were able to infer liver biopsy effects and identify additional mechanistic pharmacodynamic protein biomarkers to characterize their drug mechanism and measure response in clinical trials. “NASH and NAFLD are a significant challenge in terms of diagnosis and treatment, and the prevalence of metabolic and obesity-related diseases around the world has created a strong sense of urgency to learn more about them and find better ways of treating them,” said Standard BioTools Chief Medical Officer Stephen A. Williams, MD, PhD. “The SomaScan Assay gives us a view of the biological mechanisms of this disease with a simple blood draw from patients, and SomaSignal tests were shown in this study to be valuable in showing disease regression in patients.” The study focused on inhibiting the protein ACC1 using clesacostat, a drug that acts as an acetyl-CoA carboxylase inhibitor. Using the SomaScan Assay, researchers found 69 blood analytes that strongly correlated with clinical measures of liver inflammation and steatosis. They also discovered the expression of these analytes was significantly higher in NASH patients compared to their NAFLD counterparts. Additionally, in 231 patients in the pre-treatment phase, Standard BioTools’ SomaSignal tests were used to measure 37 different analytes that correlate with NASH and NAFLD. The tests helped researchers stratify patients by disease severity, establish a pre-treatment baseline, and monitor the effects of the drug. The 37 analytes were identified by screening thousands of patient samples using the SomaScan Assay. These analytes were shown to have critical differences in NASH and NAFLD patients and were validated against standard clinical measurements. During the 16-week trial, the SomaScan assay and SomaSignal tests were run on serum samples from study participants subjected to a once-per-day dose of clesacostat. The SomaSignal test scores aligned with improvements in liver fat content (steatosis) as measured by proton density fat fraction, or MRI-PDFF. Twenty-seven analytes were found to be significantly reversed upon drug treatment, demonstrating the utility of SomaSignal tests for classification of NASH and the ACC inhibition treatment-induced effects on steatosis. “The SomaScan Platform has been extensively and systematically validated, providing a strong foundation for this important research,” said Michael Egholm, PhD, President and Chief Executive Officer of Standard BioTools. “These researchers also used the powerful SomaSignal tests to better diagnose NASH and NAFLD patients and to study their responses to treatment.” Standard BioTools now offers the new SomaScan 11K Assay, as well as the industry leading single cell proteomics and spatial proteomics solutions (CyTOF® and Hyperion™ platforms), as a comprehensive pharma services offering to customers who are working to identify biomarkers of predictive response, mechanism of action and patient stratification in their studies. About Standard BioTools Inc. Standard BioTools Inc. (Nasdaq:LAB), the parent company of SomaLogic Inc. and previously known as Fluidigm Corporation, is driven by a bold purpose – Unleashing tools to accelerate breakthroughs in human health. Standard BioTools has an established portfolio of essential, standardized next-generation technologies that help biomedical researchers develop medicines faster and better. As a leading solutions provider, the company provides reliable and repeatable insights in health and disease using its proprietary mass cytometry and microfluidics technologies, which help transform scientific discoveries into better patient outcomes. Standard BioTools works with leading academic, government, pharmaceutical, biotechnology, plant and animal research and clinical laboratories worldwide, focusing on the most pressing needs in translational and clinical research, including oncology, immunology and immunotherapy. Learn more at standardbio.com or connect with us on X, Facebook®, LinkedIn and YouTube™. For Research Use Only. Not for use in diagnostic procedures. Limited Use Label License and other terms may apply: www.standardbio.com/legal/salesterms. Patent and License Information: www.standardbio.com/legal/notices. Trademarks: www.standardbio.com/legal/trademarks. Any other trademarks are the sole property of their respective owners. ©2024 Standard BioTools Inc. (f.k.a. Fluidigm Corporation). All rights reserved. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, among others, statements regarding future financial and business performance; expectations, operational and strategic plans; the merger of the Company and SomaLogic; deployment of capital; market and growth opportunity and potential; and the potential to realize the expected benefits following the merger of the Company and SomaLogic. Forward-looking statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from currently anticipated results, including, but not limited to, the outcome of any legal proceedings related to the merger; risks that the anticipated benefits of the merger or other commercial opportunities may otherwise not be fully realized or may take longer to realize than expected; risks that we may not realize expected cost savings from our restructuring, including the anticipated decrease in operational expenses, at the levels we expect; possible restructuring and transition-related disruption, including through the loss of customers, suppliers, and employees and adverse impacts on our development activities and results of operation; restructuring activities, including our subleasing plans, customer and employee relations, management distraction, and reduced operating performance; risks that internal and external costs required for ongoing and planned activities may be higher than expected, which may cause us to use cash more quickly than we expect or change or curtail some of our plans, or both; risks that our expectations as to expenses, cash usage, and cash needs may prove not to be correct for other reasons such as changes in plans or actual events being different than our assumptions; changes in Standard BioTools’ business or external market conditions; challenges inherent in developing, manufacturing, launching, marketing, and selling new products; interruptions or delays in the supply of components or materials for, or manufacturing of, Standard BioTools products; reliance on sales of capital equipment for a significant proportion of revenues in each quarter; seasonal variations in customer operations; unanticipated increases in costs or expenses; uncertainties in contractual relationships; reductions in research and development spending or changes in budget priorities by customers; uncertainties relating to Standard BioTools’ research and development activities, and distribution plans and capabilities; potential product performance and quality issues; risks associated with international operations; intellectual property risks; and competition. For information regarding other related risks, see the “Risk Factors” section of Standard BioTools’ most recent quarterly report on Form 10-Q filed with the U.S. Securities and Exchange Commission (the “SEC”) on November 7, 2023, on its most recent annual report on Form 10-K filed with the SEC on March 14, 2023, and in Standard BioTools’ other filings with the SEC, as well as the “Risk Factors” section of SomaLogic’s most recent quarterly report on Form 10-Q filed with the SEC on November 8, 2023, on its most recent annual report on Form 10-K filed with the SEC on March 28, 2023, and in SomaLogic’s other filings with the SEC. These forward-looking statements speak only as of the date hereof. Standard BioTools disclaims any obligation to update these forward-looking statements except as may be required by law. Media ContactEmilia Costales720 798 5054emilia.costales@standardbio.com Investors David Holmesir@standardbio.com

Phase 2Clinical Result

06 Sep 2024

·www.businesswire.com

OrsoBio Announces Oversubscribed $67 Million Series B Financing to Accelerate Mitochondrial Protonophore Portfolio Targeting Obesity and Associated Disorders

MENLO PARK, Calif.--( BUSINESS WIRE )--OrsoBio, Inc. ("OrsoBio” or “the Company”), a clinical-stage biopharmaceutical company developing treatments for obesity and obesity-associated disorders, today announced the close of an oversubscribed $67 million Series B financing. The financing was co-led by new investors Ascenta Capital and Woodline Partners LP, with significant participation from existing investors Samsara Biocapital, Longitude Capital, Enavate Sciences, NuevaBio, and Eli Lilly and Company. In conjunction with the financing, Evan Rachlin, MD, Co-Founder and Managing Partner of Ascenta Capital, has joined the OrsoBio Board of Directors. Proceeds from the financing will be used to accelerate development of the Company’s mitochondrial protonophore portfolio for the treatment of obesity and associated metabolic disorders. Obesity affects more than 40% of U.S. adults and leads to a range of adverse health outcomes including type 2 diabetes, cardiovascular disease, and metabolic dysfunction-associated steatohepatitis (MASH). Obesity is caused by an imbalance between energy intake and energy expenditure that leads to excess adiposity. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized weight management by reducing caloric intake, they may cause loss of lean mass and metabolic adaptations that reduce energy expenditure. Mitochondrial protonophores directly increase energy expenditure and may represent the ideal means to complement the metabolic benefits of GLP-1 RAs. In preclinical studies, mitochondrial protonophores developed by OrsoBio led to weight loss, preserved lean mass, and improved insulin sensitivity. Further, when these potential therapies were used in combination with a GLP-1 RA, additional weight and fat mass loss were observed, without significant effects on lean mass. These benefits were sustained with continued protonophore therapy following GLP-1 RA discontinuation. 1 TLC-6740 is a novel, oral, liver-targeted mitochondrial protonophore under evaluation in a 12-week, Phase 1b clinical trial in patients living with obesity ( NCT05822544 ). In a prior Phase 1 study in healthy subjects, TLC-6740 was safe, well tolerated, and caused dose-dependent increases in energy expenditure and improvements in lipids and markers of insulin resistance. Additional Phase 1b and Phase 2a studies of TLC-6740 in patients with obesity and type 2 diabetes, including those on a GLP-1 RA, will initiate in the coming months. IND-enabling studies for two additional novel protonophores (TLC-1180 and TLC-1235) with unique attributes compared to TLC-6740, including greater systemic distribution, are expected to be completed in 2025. TLC-1180 is a potent, long-acting mitochondrial protonophore that is suitable for weekly oral or subcutaneous administration. TLC-1235 is a controlled-release mitochondrial protonophore (CRMP) that has shown metabolic benefits across a range of models and species. 2 "We welcome Ascenta Capital and Woodline Partners to OrsoBio and appreciate their support and that of our existing investors. These resources enable us to continue advancing our portfolio of mitochondrial protonophores and other potential therapies to address the burden of obesity and obesity-associated diseases,” said Mani Subramanian, MD, PhD, CEO and Founder of OrsoBio. “We believe that the future of obesity treatment will include GLP-1 RA-based combinations; this financing will enable us to build the scientific and clinical foundations to support our protonophores as components of these regimens.” "OrsoBio’s novel mechanisms hold promise to enhance weight loss, improve metabolic function, and preserve lean muscle mass,” said Evan Rachlin, MD, Co-Founder and Managing Partner of Ascenta Capital. “These medicines could one day complement GLP-1 RA-based approaches and expand the long-term health benefits of these treatments. We look forward to partnering with the world-class team at OrsoBio to help bring these extraordinary medicines to patients.” OrsoBio’s portfolio of compounds in clinical development also includes TLC-3595, an ACC2 inhibitor, currently in a Phase 2a study for the treatment of type 2 diabetes, and TLC-2716, a liver X receptor (LXR) inverse agonist currently in a Phase 2a study for severe hypertriglyceridemia and MASH. About OrsoBio, Inc. OrsoBio, Inc. is a privately held, clinical-stage biopharmaceutical company dedicated to developing therapies to treat obesity and obesity-associated disorders, including type 2 diabetes, MASH, and severe dyslipidemias. OrsoBio currently has four programs in clinical and preclinical development with first-in-class compounds that address central pathways in energy metabolism. For more information, please visit www.orsobio.com . ____________________________ 1 Data accepted for presentation at ObesityWeek® 2024. 2 Perry RJ, et al. Science 2015 ( PMID: 25721504 ); Goedeke L, et al. Mol Metab 2021 ( PMID: 33545391 ).

Phase 1Phase 2

21 Jun 2024

·www.biospace.com

OrsoBio to Present Phase 1 and Preclinical Data for Liver-Targeted Mitochondrial Protonophore TLC-6740 at the American Diabetes Association’s 84th Scientific Sessions

Phase 1 data confirm the safety of TLC-6740, dose-dependent increases in energy expenditure, and improvements in plasma lipids and markers of insulin resistance Preclinical data confirm increased energy expenditure and weight loss with TLC-6740, and the potential of combination treatment with GLP-1 receptor agonists and the company’s ACC2 inhibitor TLC-3595 MENLO PARK, Calif.--(BUSINESS WIRE)-- OrsoBio, Inc., a clinical-stage biopharmaceutical company developing treatments for obesity and obesity-associated disorders, today announced new data for liver-targeted mitochondrial protonophore TLC-6740 being presented at the 84th Scientific Sessions of the American Diabetes Association being held June 21-24, 2024, in Orlando, Fla. The company will present three abstracts sharing new data demonstrating the safety and preliminary efficacy of its mitochondrial protonophore, TLC-6740, in healthy humans, and preclinical data highlighting weight loss driven by increased energy expenditure and improved glycemic control in mouse models following monotherapy and combinations with the selective ACC2 inhibitor, TLC-3595, and a GLP-1 receptor agonist. “Our Phase 1 data illustrate the potential of our liver-targeted mitochondrial protonophore, TLC-6740, to enable safe increases in energy expenditure, metabolic benefits, and to promote weight loss in people living with obesity,” said Rob Myers, MD, Chief Medical Officer of OrsoBio. “In light of our new clinical and preclinical data, we look forward to advancing TLC-6740 to treat obesity and its comorbidities, including in combination with GLP-1 receptor agonists.” Increasing cellular energy expenditure by mitochondrial uncoupling is a validated approach to weight loss. By targeting the liver—a key organ governing whole-body energy metabolism—TLC-6740 has demonstrated substantial weight loss in rodents driven by increased energy expenditure and fat oxidation. These new Phase 1 data confirm the safety of TLC-6740 in humans and demonstrate clinically relevant increases in energy expenditure, utilization of fat for energy, and multiple metabolic benefits, including improvements in LDL cholesterol, total cholesterol, markers of insulin resistance, and liver biochemistry. Further, data from preclinical models of diabetes suggest that combining TLC-6740 and drugs with complementary mechanisms, including the ACC2 inhibitor, TLC-3595, and the GLP-1 receptor agonist, semaglutide, can have additive benefits on insulin resistance. “With the growing burden of obesity-related disorders, it’s critical that new, safe, effective therapies be developed to complement existing medications, such as GLP-1 receptor agonists,” said Gerald Shulman, MD, PhD, MACP, MACE, FRCP, the George R. Cowgill Professor of Medicine and Professor of Cellular and Molecular Physiology at Yale School of Medicine, Co-Director of the Yale Diabetes Research Center, and scientific advisor to OrsoBio. “These human and preclinical data highlight the promise of TLC-6740 to promote healthy weight loss by driving increased energy expenditure and fat oxidation, and directly address the root cause of insulin resistance, which drives many of the complications of obesity.” ADA Presentation Details Abstract #1186-LB: Safety, PK and preliminary efficacy of the liver-targeted mitochondrial protonophore TLC-6740: A Phase 1 study Late-Breaking Poster Session: Saturday, June 22, 2024 (12:30 – 1:30 p.m.) This randomized, double-blind Phase 1 trial (NCT05822544) was designed to evaluate the safety, tolerability, PK, and pharmacodynamics of single and multiple ascending doses of TLC-6740 (3-120 mg) in healthy subjects. OrsoBio previously presented data from the SAD cohorts at ObesityWeek® 2023, and new data from MAD cohorts confirmed the safety of TLC-6740 administered for 10 days. All TLC-6740-related adverse events were mild, and there were no drug-related discontinuations, lab abnormalities, or temperature increases. The PK pro TLC-6740 includes a prolonged half-life (18 to 33 hours), supporting once-daily, oral dosing. In addition, indirect calorimetry demonstrated significant, dose-dependent increases in resting energy expenditure and reductions in respiratory quotient (RQ), indicating a preference for oxidation of fat for energy, with TLC-6740 treatment. Finally, TLC-6740 caused dose-dependent improvements in serum total and LDL cholesterol, markers of insulin resistance, and liver biochemistry. Abstract #899-P: Combinations of the mitochondrial protonophore TLC-6740 and/or the ACC2 inhibitor TLC-3595 provide additive glycemic benefits to semaglutide (SEMA) in db/db mice Poster Session: Sunday, June 23, 2024 (12:30 – 1:30 p.m.) This preclinical study assessed the effects of TLC-6740, TLC-3595, and semaglutide in the db/db mouse model of diabetes. Mice were treated with these compounds as monotherapy, or a combination of either two or three of these agents, and fasting blood glucose (FBG), HbA1c, and glucose during an oral glucose tolerance test were measured. All groups saw reductions in FBG and HbA1c; the greatest reductions were observed in groups treated with combination therapy. Both TLC-6740 and TLC-3595 improved glycemic parameters as monotherapy and had additive benefits when combined with each other and semaglutide. These data provide evidence to support the continued evaluation of TLC-6740 and TLC-3595 as monotherapy and in combination with GLP-1 receptor agonists as potential treatments for type 2 diabetes. Abstract #1637-P: TLC-6740, a liver-targeted mitochondrial protonophore, increases energy expenditure and lipid utilization in obese mice Poster Session: Monday, June 24, 2024 (12:30 – 1:30 p.m.) This preclinical study evaluated mechanisms of weight loss with TLC-6740 treatment in diet-induced obese (DIO) mice. Body weight and energy (food) intake were monitored, and energy expenditure was measured by indirect calorimetry. The data showed that TLC-6740 increased energy expenditure by ~20%, without altering food intake, thereby inducing a negative energy balance, and causing weight loss. In addition, TLC-6740 decreased RQ, indicating increased fat oxidation, consistent with data observed in the Phase 1 human study, and supporting continued development of TLC-6740 for the treatment of obesity. About TLC-6740 TLC-6740 is a novel, oral, liver-targeted mitochondrial protonophore in development for the treatment of obesity and obesity-associated diseases, including diabetes and MASH. Based on active hepatic uptake and mitochondrial protonophore activity, TLC-6740 increases energy expenditure in hepatocytes, and is expected to have broad, systemic metabolic and cardiovascular benefits, including weight loss, and improved insulin sensitivity, MASH, and dyslipidemia. TLC-6740 is currently being evaluated in a 12-week, Phase 1b clinical trial in patients living with obesity (NCT05822544). About TLC-3595 and ACC2 Inhibition TLC-3595 is a novel and selective ACC2 inhibitor designed to treat type 2 diabetes by increasing fatty acid oxidation (FAO), reducing ectopic lipid accumulation, and improving insulin sensitivity in skeletal muscle and liver. The compound may also have potential as a treatment for other conditions characterized by impaired FAO, including cirrhosis with myosteatosis-associated sarcopenia and MASH. TLC-3595 is currently being evaluated in a 12-week, Phase 2a clinical trial in patients with insulin resistance and type 2 diabetes (NCT05665751). About OrsoBio, Inc. OrsoBio, Inc. is a privately held, clinical-stage biopharmaceutical company dedicated to developing therapies to treat obesity and obesity-associated disorders, including type 2 diabetes, MASH, and severe dyslipidemias. OrsoBio currently has four programs in clinical and preclinical development with first-in-class compounds that address central pathways in energy metabolism. For more information, please visit .

Phase 1Phase 2Clinical Result

100 Deals associated with S-723595

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 2	-	Orsobio, Inc.Startup	04 Jul 2023
Insulin Resistance	Phase 2	NZ	Orsobio, Inc.Startup	08 Mar 2023
Nonalcoholic Steatohepatitis	Phase 1	JP	Shionogi & Co., Ltd.	10 May 2021

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