Bimagrumab

MTRX31 led to a highly significant decrease in fat mass after two-months chronic dosing in a preclinical diet-induced obesity mouse model performed at thermoneutrality Weight loss and reduction of fat deposits in multiple organs (ectopic fat) was observed with MTRX31, comparable to combinations of current modalities (GLP-1RA, GIP, ActR) while improving circulating and tissue metabolic parameters (FFA, TG, HDL/LDL, glucose, insulin) Treatment with MTRX31 improved muscle function and did not lead to lean mass loss MTRX31 showed superiority to tirzepatide (5nmol/kg) and bimagrumab in the study when administered as a monotherapy MTRX31 did not affect calorie intake and did not demonstrate the habituation phenomenon observed with tirzepatide or bimagrumab, suggesting a durable impact on weight loss Harwell Oxford, UK – 8 June 2026 : MitoRx Therapeutics (“MitoRx”), a biotech company targeting the restoration of healthy mitochondrial metabolism in high-risk obesity, announces preclinical data for its lead asset, MTRX31, was presented at the American Diabetes Association’s 2026 Scientific Sessions (ADA 2026), taking place in New Orleans, Louisiana from 5-8 June. MTRX31 is a novel small molecule that aims to eliminate ectopic fat from affected organs by resetting mitochondrial function rather than suppressing appetite, restoring healthy mitochondrial metabolism by resetting the balance between fat and carbohydrate oxidation. The data was generated from a study using a diet-induced obesity (DIO) mouse model and was presented in a poster entitled “Myo-004 (MTRX31) induces bodyweight loss in DIO at thermoneutrality by switching metabolism from fat to carbohydrate oxidation” by Xavier Jacq, Chief Scientific Officer of MitoRx Therapeutics. In the study, MTRX31 led to a highly significant reduction in fat mass after two months of dosing, and decreased abnormal fat build-up in various tissues such as the liver and pancreas (ectopic fat). The degree of this effect was comparable to combinations of current modalities (GLP-1RA, GIP, ActR) while MTRX31 also improved circulating and tissue metabolic parameters as well as insulin sensitivity and glucose tolerance, indicating a broader positive effect on metabolic health than weight loss alone. In terms of body weight loss, MTRX31 generated a 38.4% reduction in weight (versus vehicle control) while tirzepatide, the dual GLP-1RA/GIP agonist, generated only a 29.7% reduction. The combination of MTRX31 with tirzepatide generated 50.64% body weight loss. In terms of fat loss, MTRX31 is even more impressive and generated 62.2% fat loss versus vehicle as a monotherapy. MTRX31 did not affect calorie intake and did not demonstrate the habituation phenomenon observed with tirzepatide or bimagrumab, suggesting a long-lasting and durable impact on weight loss. MTRX31 weight loss did not lead to any lean mass loss while tirzepatide displayed some previously reported slight decrease in lean mass. Furthermore, in an acute grip strength evaluation at the end of the two-month treatment period, MTRX31 demonstrated improvements in muscle strength while tirzepatide and bimagrumab did not. Xavier Jacq, PhD, Chief Scientific Officer, MitoRx Therapeutics commented: “ These exciting data demonstrate the potential for MTRX31 to address multiple challenges faced by current obesity treatments. In this study, MTRX31 demonstrated a significant reduction in body weight and ectopic fat deposits, while improving circulating and tissue metabolic parameters, without the lean mass loss often seen with currently available treatments. Further evaluation is ongoing to characterize the benefits provided by MTRX31 and its use for the treatment of metabolically unhealthy obesity.” Jon Rees, PhD, CEO of MitoRx Therapeutics added: “ Mitochondrial dysfunction and loss of mitochondrial health in obesity is associated with progression into serious diseases such as type 2 diabetes, MAFLD/MASH and atherosclerotic cardiovascular disease. These data, generated in an industry-standard preclinical model, suggests that MTRX31 could provide an alternative mode-of-action to combat metabolically unhealthy obesity at root cause, generating fat-specific weight loss that preserves lean mass and helps prevent serious cardiometabolic comorbidities . We look forward to progressing the program into the clinic in due course.” During the course of the two-month study, no adverse effects were observed in monotherapy or in combination with tirzepatide. From a pathology perspective, no observations were detected in any organs examined (heart, liver, pancreas, muscles, white adipose tissue, brown adipose tissue beyond improvements in adiposity. Circulating levels of alanine aminotransferase and aspartate aminotransferase were significantly improved by treatment with MTRX31, reflecting less liver toxicity. The poster with the full data from the ADA presentation is available on the MitoRx website in the News & Events section. - Ends - About MitoRx Therapeutics MitoRx is a biotech company targeting the restoration of healthy mitochondrial metabolism in high-risk obesity. This is critical for the 30-40% of patients living with metabolically unhealthy obesity – characterized by visceral adiposity and insulin resistance involving mitochondrial dysfunction – who are at disproportionate risk of metabolic-associated fatty liver disease, metabolic-associated steatohepatitis, type 2 diabetes and atherosclerotic cardiovascular disease. Our first-in-class small molecule asset, MTRX31, targets the elimination of ectopic fat from affected organs by resetting mitochondrial function rather than suppressing appetite. This has the potential to deliver durable and higher quality weight loss, with implications for lower risk of cardiovascular complications and other serious disease, as well as benefits for body composition and improved quality of life. Preclinical studies showed high-dose MTRX31 driving significant weight loss that outperformed tirzepatide in magnitude, quality and durability after two months of treatment. Find out more about our work on LinkedIn or visit our website at mitorxtherapeutics.com . For more information about MitoRx Therapeutics, please contact: MitoRx Therapeutics info@mitorxtherapeutics.com ICR Healthcare Tracy Cheung, Ashley Tapp, Phillip Marriage mitorx@icrhealthcare.com

Cambridge, MA, Rotterdam, NL, Shanghai, CN — May 18, 2026 Harbour BioMed (the "Company"; HKEX: 02142), a global biopharmaceutical company committed to the discovery and development of novel antibody therapeutics in immunology, oncology and other disease areas, today announced preclinical data for LET003, its first next-generation ACVR2A/2B-targeting monoclonal antibody developed using the Hu-mAtrIx™ platform. The results showed that LET003 exhibited superior pharmacokinetic characteristics compared to multiple competitor molecules. When combined with semaglutide, LET003 significantly enhanced fat reduction while effectively preserving lean mass. In addition, LET003 achieved lean mass-promoting effects at lower dose level comparable to bimagrumab at higher dose level, highlighting its potential to become a best-in-class therapy for obesity treatment. The ACVR2A/2B signaling pathway plays a critical role in regulating the balance between fat and muscle mass in the body. Previously, bimagrumab, the first antibody targeting ACVR2A/2B, demonstrated positive clinical results, showing favorable efficacy and safety in combination with semaglutide for obesity treatment. Building on these findings, Harbour BioMed successfully advanced the molecular optimization and functional enhancement of LET003 through structure biology and Hu-mAtrIx™ , its AI platform-driven antibody engineering approaches. In human FcRn transgenic mouse and cynomolgus monkey models, researchers compared the blood clearance rates of LET003 with several competing molecules following subcutaneous administration. Results showed that LET003 exhibited significantly slower clearance than all comparator molecules tested, suggesting that it may achieve comparable efficacy with longer dosing intervals or lower doses relative to competing therapies. In an obesity model using wild-type mice, semaglutide (30 nmol/kg) and LET003 (20 mg/kg) were administered subcutaneously once weekly as monotherapies or in combination. Results after three weeks of treatment showed: LET003 in combination with semaglutide decreased fat mass by 76.0% compared with vehicle (P<0.0001), and by 34.7% compared with semaglutide monotherapy (P<0.0001). In the combination group, lean mass decreased by 6.5% compared with vehicle (P=0.0001), but increased by 5.7% compared with semaglutide monotherapy (P=0.0007). These data suggest that combining LET003 with semaglutide can significantly enhance fat reduction while effectively mitigating the lean mass loss associated with semaglutide treatment alone. In a high-fat diet-induced obesity model using human FcRn transgenic mice, semaglutide (30 nmol/kg) and LET003 (20 mg/kg) were administered subcutaneously once weekly as monotherapies or in combination. Results after three weeks of treatment showed: The fat-to-body weight ratio in the combination group was reduced by 17.5% compared with vehicle (P<0.0001), and by 6.0% compared with semaglutide monotherapy (P=0.0127). The lean mass-to-body weight ratio in the combination group was increased by 15.2% compared with vehicle (P<0.0001), and by 5.3% compared with semaglutide monotherapy (P=0.0194). These data further confirm that combining LET003 with semaglutide not only more effectively reduces body fat proportion, but also significantly improves lean mass ratio, enabling superior body composition management. In a separate study using human FcRn transgenic mice maintained on a normal diet, mice received weekly subcutaneous injections of LET003 or a comparator molecule at 20 mg/kg. After three weeks of treatment, both molecules induced an increase in lean mass and a consequent increase in overall body weight. Specifically: The LET003 treatment group showed an 18.3% increase in lean mass compared with vehicle (P<0.0001), and a 13.5% increase compared with the comparator molecule (P<0.0001). The LET003 treatment group showed an 11.1% increase in overall body weight compared with vehicle (P < 0.0001), and a 9.3% increase compared with the competitor molecule (P < 0.0001). These findings suggest that LET003 is superior to the competitor molecule in promoting lean mass. In another study using human FcRn transgenic mice maintained on a normal diet, mice received weekly subcutaneous injections of bimagrumab or LET003 at different dose levels (5 mg/kg, 10 mg/kg, and 15 mg/kg). The results showed that both molecules contributed more to the increase in lean mass than to fat accumulation. After three weeks of treatment, LET003 at 5 mg/kg achieved lean mass-promoting effects comparable to those observed with 15 mg/kg bimagrumab. These results suggest that LET003 can achieve lean mass-promoting effects at lower dose level comparable to bimagrumab at higher dose level, demonstrating its excellent pharmacological potential. "The rapid advancement of LET003 has been strongly supported by our Hu-mAtrIx™ AI platform. Built on data generated from our proprietary Harbour Mice® platforms, Hu-mAtrIx™ integrates fine-tuned large language models for sequence generation together with highly accurate AI classification and developability prediction models," said Dr. Jingsong Wang, Founder, Chairman and Chief Executive Officer of Harbour BioMed. "We are highly encouraged by the favorable pharmacokinetic profile demonstrated by LET003 in preclinical studies, as well as its potential in fat reduction and lean mass preservation. These findings further validate our technological capabilities in AI-driven antibody engineering and metabolic disease research. We look forward to rapidly advancing LET003 into clinical development and providing obesity patients worldwide with more effective and safer treatment options." About LET003 LET003 is a potential best-in-class next-generation monoclonal antibody targeting activin receptors ACVR2A and ACVR2B. ACVR2A and ACVR2B play critical roles in regulating muscle-fat metabolic homeostasis. Extensive preclinical and clinical studies have demonstrated that combining receptor-blocking antibodies targeting ACVR2A/2B with GLP-1-based weight loss therapies can further reduce body fat while effectively mitigating lean mass loss. LET003 is the first ACVR2A/2B dual-target blocking antibody developed using the Hu-mAtrIx™ artificial intelligence platform. It has demonstrated superior pharmacokinetic properties compared with several competing molecules and, in preclinical animal models, has shown enhanced fat reduction and lean mass preservation effects when used in combination with GLP-1 therapies. About Harbour BioMed Harbour BioMed (HKEX: 02142) is a global biopharmaceutical company committed to the discovery and development of novel antibody therapeutics in immunology, oncology and other areas. The Company is building a robust portfolio and differentiated pipeline through internal R&D capability, strategic global collaborations in co-discovery and co-development, and selective acquisitions. Our proprietary antibody technology platform, Harbour Mice®, generates fully human monoclonal antibodies in both the conventional two heavy and two light chain (H2L2) format and the heavy chain-only (HCAb) format. Building upon HCAb antibodies, the HCAb-based immune cell engagers (HBICE®) bispecific antibody technology enables tumor-killing effects that traditional combination therapies cannot achieve. The HCAb-based Antibody Plus technology (HCAb PLUS™ ) provides comprehensive modality solutions for the development of innovative multi-specific medicines in different disease areas. Additionally, building upon the Harbour Mice® platform, Harbour BioMed launched its first fully human Generative AI HCAb Model powered by its Hu-mAtrIx™ AI platform, accelerating the development of innovative therapies. By integrating Harbour Mice®, HBICE®, HCAb PLUS™ , a single B-cell cloning platform and AI technologies, Harbour BioMed has built a highly efficient and distinctive antibody discovery engine for developing next-generation therapeutic antibodies. For more information, please visit www.harbourbiomed.com.